Lynch entered the NFL as the starter at running back for the Bills. In his first career regular season game on September 9, he gained 90 yards on 19 carries and scored his first touchdown in a 14–15 loss to the Denver Broncos. His breakout game came on November 4 against the Cincinnati Bengals. Lynch's success on the ground was instrumental in keeping the touted Cincinnati offense on the sidelines, as he rushed 29 times for 153 yards, including a 56-yard touchdown run. Lynch also completed a touchdown pass to tight end Robert Royal, the first touchdown pass completed by a Bills non-quarterback since running back Joe Cribbs in 1981.
Lynch injured his ankle the following week against the Miami Dolphins and missed the next three games. He returned to play on December 9 for the Bills' second game against the Miami Dolphins that season, rushing for 107 yards and fumbling for the first time in his NFL career. The game marked the first time the Bills' offense produced two 100-yard rushers since 1996, as Fred Jackson also rushed for 115 yards. Lynch went over the 1,000-yard rushing mark on December 23 against the New York Giants, scoring a touchdown in the 21–38 loss, which resulted in the Giants clinching a playoff berth. This made Lynch the fourth Bills rookie to break the 1,000-yard mark, and the first since Greg Bell in 1984. He closed out the regular season with 105 rushing yards and 22 receiving yards against the Philadelphia Eagles. He finished a successful rookie season with 1,115 total rushing yards and seven touchdowns. He was named to the NFL All-Rookie Team for the 2007 season.
Lynch started the 2008 season with four rushing touchdowns in his first three games against the Seattle Seahawks, Jacksonville Jaguars, and Oakland Raiders. He was held to a season low of 16 yards rushing in a Week 9 matchup against the New York Jets on November 2. He did not break 100 yards rushing in a game until November 17 on a Monday Night Football matchup against the Cleveland Browns, when he rushed for 119. The game also marked his first receiving touchdown. Two weeks later on November 30, Lynch posted a season-high 134 rushing yards against the San Francisco 49ers. Lynch went over the 1,000-yard mark for the season on December 14 in a rematch against the Jets when he rushed for 127 yards. He was able to stay healthy until injuring his shoulder in the second half of a Bills victory on December 21 against the Denver Broncos, during which he rushed for his eighth touchdown of the season. The injury kept him out of the Bills' season finale against the New England Patriots. Lynch finished the 2008 season with 1,036 yards rushing and eight rushing touchdowns. He posted 300 receiving yards on 47 receptions, including a receiving touchdown, compared to 184 yards on 18 receptions for the 2007 season. Lynch was selected to his first Pro Bowl, replacing injured Tennessee Titans running back Chris Johnson. This made him the first Bills running back to head to the Pro Bowl since Travis Henry in 2002. Lynch was initially the first alternate.
As a true freshman in 2004, Lynch was the primary backup to senior J. J. Arrington. In his collegiate debut against Air Force in the regular season opener, he had seven carries for 92 yards and a touchdown in the 56–14 victory. On November 13, in the 42–12 victory over Washington, he had nine carries for 121 rushing yards and two rushing touchdowns to go along with a 29-yard touchdown reception. One week later, against Stanford, Lynch had 122 rushing yards and one rushing touchdown. In addition, he threw a 20-yard touchdown pass to Burl Toler in the 41–6 victory. Overall, Lynch carried the ball 71 times for 628 yards with eight rushing touchdowns and 147 yards on 19 receptions and two receiving touchdowns in his freshman season.
In 2005, Arrington had graduated and Lynch became the starting running back.Lynch wore jersey No. 24 his freshman year but switched to No. 10, his high school number. This switch placed him in sequence with his cousins Virdell Larkins, who wore No. 9, and Robert Jordan, who wore No. 11. Lynch and his cousins were teammates at Cal. Lynch started off the season strong with 24 carries for 147 rushing yards and a rushing touchdown in the 41–3 victory over Sacramento State. Almost a month later, on October 1, he had 107 rushing yards and a rushing touchdown in a 28–0 victory over Arizona. The next week, he had 135 rushing yards and a rushing touchdown in the 47–40 loss to UCLA. On October 22, against Washington State, he had 160 rushing yards and a rushing touchdown in the 42–38 loss. In the next game, a 27–20 loss to Oregon, he had 189 rushing yards and two rushing touchdowns. In the regular season finale against the Stanford Cardinal, he had 123 rushing yards and a rushing touchdown in the 27–3 victory. In the 2005 Las Vegas Bowl, Lynch ran for 194 yards and three touchdowns on 24 carries and was named MVP against BYU. Even though he missed two games due to a hand and finger injury, he still amassed 1,246 rushing yards with 10 rushing touchdowns on 196 carries and 125 receiving yards on 15 receptions. He finished fifth in the Pac-10 in rushing yards and sixth in rushing touchdowns.
On November 6, against the Dallas Cowboys, Lynch had 135 rushing yards and a touchdown. On December 11, he had his best rushing game of the season with 148 rushing yards and two rushing touchdowns against the Philadelphia Eagles. On December 18, he set the franchise record for consecutive games with a touchdown by scoring in his tenth straight game. The previous record of nine was set by Shaun Alexander in 2005. Lynch would reach 11 consecutive games scoring a touchdown before the streak ended against the Arizona Cardinals in Week 17. Lynch led the NFL in rushing yards over the final nine weeks of the season. On January 24, 2012, Lynch was added to the NFC Pro Bowl roster to replace San Francisco 49ers running back Frank Gore. He was ranked 94th by his fellow players on the NFL Top 100 Players of 2012.
In the second game of the season, against Minnesota, Lynch had 139 rushing yards and two rushing touchdowns in the 42–17 victory In the next game against Portland State, he finished with 112 rushing yards and a touchdown in the 42–16 victory. In the following game against Arizona State, he had 17 carries for 124 yards in the 49–21 victory. In the next game, against Oregon State, he posted his fourth consecutive 100-yard game with 106 yards and a touchdown in the 41–13 victory. After a 50-yard performance in the 45–24 victory over the Oregon Ducks, he had 152 rushing yards and two touchdowns in the 21–3 victory over Washington State. In the next game against Washington, he had another stellar game with 150 rushing yards and two touchdowns, including the game-winning overtime touchdown, in the 31–24 victory. He later called the run his favorite career highlight, after which Lynch spontaneously drove around the football field in an injury cart, pretending to ghost ride. Lynch was named to the 2006 All-Pac-10 team First Team for his performance in the 2006 season. Lynch was also named the Pac-10 Offensive Player of the Year in 2006 and an AFCA (Coaches') All-America in 2006.
On July 22, 2006, the Cal football program officially launched the campaign for Lynch to win the 2006 Heisman Trophy with the opening of the website Marshawn10.com, featuring Lynch's highlights from 2004 to 2006.
In his final game for Cal, Lynch ran for 111 yards and two touchdowns in the 45–10 victory over Texas A&M in the Pacific Life Holiday Bowl on December 28, 2006. He shared the Co-Offensive Player of the Game award with teammate, quarterback Nate Longshore. He finished his final season with Golden Bears with a Pac-10 leading 1,356 rushing yards, 11 rushing touchdowns, 34 receptions, 328 receiving yards, and four receiving touchdowns.
On January 2, 2007, Lynch announced he would forgo his senior season and enter the 2007 NFL Draft.
On April 28, 2007, Lynch was selected by the Buffalo Bills with the 12th overall pick in the first round of the NFL Draft, the second running back taken. He agreed with the Bills to a six-year, $18.935 million contract. The deal included a $3 million signing bonus and contained $10.285 million in total guarantees.
Lynch then reunited with former Cal roommate and fellow running back Justin Forsett, a seventh-round draft pick of the Seahawks in 2008. Lynch scored his first touchdown of the season and with the Seahawks on October 17 on a 1-yard run against the Chicago Bears. On December 5, he scored three touchdowns against the Carolina Panthers.
Lynch was expected to be more involved in Buffalo's passing game in 2008, his second season as a professional. The Bills' new offensive coordinator Turk Schonert had stated a number of times that he anticipated Lynch "being in on third down a lot more" this season, citing Lynch's inexperience as a reason he was not very involved in the 2007 season.
In June 2008, Lynch pled guilty to a hit and run charge and had his driver's license revoked. Lynch was driving his 2008 Porsche Cayenne at 3:30 a.m. through Buffalo's bar district when he struck a woman in the street and failed to stop. When questioned, Lynch stated, "I didn't know my car had hit anyone or anything."
Lynch started 15 games in 2011, missing only one regular season game, on November 23 due to back problems. Lynch rushed for 1,204 yards and 12 touchdowns, both career bests and posting his first 1,000-yard season since 2008. On December 1, against the Philadelphia Eagles, he was observed receiving Skittles from a trainer to celebrate his touchdown. Fans later threw Skittles onto the field after Lynch scored.
In his first career playoff game, against the New Orleans Saints on January 8, 2011, Lynch had a 67-yard touchdown run in which he broke nine tackles and with one arm threw Saints cornerback Tracy Porter to the ground. This run has become known locally in Seattle as the "Beast Quake". The play gets its name from Marshawn Lynch's nickname, "Beast Mode", and the fact that, during and after the play, movement from fans jumping in celebration was so intense that it registered on a seismograph 100 yards from the stadium. In the Divisional Round against the Chicago Bears, he was limited to four carries for two yards in the 35–24 loss. Lynch had a total of 737 yards and six touchdowns during the 2010 season.
Lynch frequently ate Skittles during games, a habit which started when he was in high school. After Lynch was shown eating the candy during a nationally televised game on December 5, 2011, Mars offered him a two-year supply of Skittles and a custom dispenser for his locker. On December 30, 2011, he was fined $10,000 for wearing cleats featuring a Skittles pattern. On January 28, 2014, an official deal with Skittles was announced. The agreement stated that in addition to personal compensation, $10,000 would be donated to his Fam First Foundation for each touchdown he scored in Super Bowl XLVIII.
On March 4, 2012, Lynch signed a four-year, $31 million contract with the Seahawks.
Lynch was arrested on July 14, 2012, by the California Highway Patrol for DUI after he was observed driving erratically. He was reported to have registered a 0.10 on the Breathalyzer at Alameda County Sheriff's Office North County Jail in Oakland. He was incarcerated hours before hosting a youth football camp. A motion to dismiss the case was denied in November 2013, but in December the trial date was pushed back until after the NFL season. Lynch's attorney, Ivan Golde, accused the police of bending the truth and changing stories to try to convict Lynch. The case was settled in February 2014 when Lynch pleaded guilty to a lesser charge of reckless driving. Lynch received two years of probation and a $1,033 fine, and had to attend drivers' safety classes, but did not have his license suspended.
While in Buffalo, Lynch embraced the Buffalo community, in stark contrast to former Bills running back Willis McGahee, as noted in an interview with ESPN's Kenny Mayne. In the video interview, which has become an internet sensation, Lynch talks about his love of Applebee's, and his teammates joke that he loves chain restaurants. Lynch is also known for his frequent community involvement. In 2013, he was featured in Red Bull's campaign "Athletes Give Back" when he put together a successful food drive for his hometown.
On July 24, 2014, former Seahawks fullback and good friend Michael Robinson announced on NFL Network's Inside Training Camp, that Lynch would hold out of Training Camp while he waited for a restructured contract from the Seahawks. Lynch and the Seahawks quickly agreed to new terms for the season, and Lynch served as the starting running back for the team, ahead of backups Robert Turbin and Christine Michael.
Lynch is known for being reluctant to talk to the media. He was fined $50,000 by the NFL for refusing to talk to the media throughout the 2013 NFL season, which inspired fans of the Seattle Seahawks to fundraise that amount. However, the fine was subsequently pulled back in an agreement that he would be fined another $50,000 if he broke the same rule, after which he donated the money raised by Seahawks fans to pay his fine to charity. Lynch was fined $100,000 on November 19, 2014, for once again refusing to speak to the media. A few days later, after the Seahawks' win over Arizona, he answered nearly every question from reporters with "Yeah". On December 21, 2014, after the second Seahawks–Cardinals game, he answered nearly every question from reporters with some version of "Thanks for asking" or "I appreciate you asking." The only people to get an "extended interview" were Deion Sanders, former teammate turned analyst Michael Robinson, and Michael Silver, in which they discovered his reluctance came from his upbringing and the fact that he felt that he was "forced to do something." On January 27, 2015, during Super Bowl Media Day in Glendale, Arizona, Lynch continued the trend of declining to give detailed media interviews by showing up for five minutes, and answering every question with some variation of "I'm just here so I won't get fined," and the following day "You know why I'm here."
Lynch made headlines at Super Bowl XLIX Media Day on January 27, 2015, when he held a five-minute press conference, only answering "I'm just here so I won't get fined" to every question. He has a history of unwillingness to talk to the media.
On March 6, 2015, the Seahawks and Lynch agreed to a 2-year, $24 million contract extension. Lynch struggled to pile up yardage early in the season but starred in Week 7 in a 20–3 win over the rival San Francisco 49ers, against whom he racked up 122 yards and a touchdown on 27 carries. Midway through the 2015 season, Lynch needed to have sports hernia surgery. Lynch's backup, undrafted rookie Thomas Rawls, had a 209-yard game against the 49ers in Week 11.
Lynch has since developed the nickname into his Beast Mode brand, which includes an apparel line, retail store, and at least one partnership with international brands. The first Beast Mode store opened in Oakland, California on February 7, 2016, during Super Bowl 50. On April 8, 2015, rapper Ludacris released the video for his single "Beast Mode," named after Lynch, who appears in the video. Ludacris mimics Lynch's interview at the Super Bowl media day by saying "I'm just here so I won't get fined" to reporters before Lynch comes in and adds "You know why we here". Lynch makes a cameo in the video game Call of Duty: Black Ops III. He also appeared in the fourth episode of the sixth season of Tanked where they created a special fish tank for "BeastMode" first aired June 19, 2015.
One week before the Seattle Seahawks' first pre-season game of 2015, it was announced that Lynch would appear in the Season 7 premiere episode of FX's The League, as himself on September 9, 2015. That same day, Entertainment Weekly released a video clip of the cameo appearance in which Lynch argues to one of the show's main characters that he's "so close" to another character he can "just run [a beer] over to him" instead of tossing it, a reference mocking the infamous call to throw the ball to the middle of the field in the final 30 seconds of Super Bowl XLIX.
On February 7, 2016, the day of Super Bowl 50, Lynch announced his retirement via Twitter by posting a picture of his football cleats hanging from a telephone wire. He subsequently became a mentor to the current college football players at Cal.
After his retirement, rumors circulated about Lynch returning to the NFL. In early April 2017, after sitting out the 2016 season, it was reported Lynch had agreed to terms with his hometown Oakland Raiders and that the Seahawks, who retained his rights even after retirement, would trade him. Lynch said he was inspired to come out of retirement by the team's impending move to Las Vegas saying that he wanted children currently growing up in Oakland to be able to see a home-grown football star play for the Raiders before the team is gone.
On April 26, 2017, Lynch officially passed his physical and was traded to the Oakland Raiders along with Seattle's sixth-round draft pick for Oakland's fifth-round selection in the 2018 NFL Draft. Lynch then signed a two-year, $9 million contract with a max of up to $16.5 million; it had a $2 million bonus for 1,000 rushing yards for the season.
On September 19, 2017, Lynch launched his own ad-supported Beast Mobile cellphone service that allows subscribers to pay their phone bill by engaging in ads and offers.
In 2019, Lynch was announced as co-owner of the Oakland Panthers of the Indoor Football League alongside by Roy Choi, who also owns the IFL's Cedar Rapids River Kings and San Diego Strike Force. Introduced to Choi by his brother Davonte Sapp-Lynch who plays in the IFL, Lynch sees the arena football team as a way to keep professional football in Oakland after the departure of the Raiders for Las Vegas.
He played a spoof of himself in the Brooklyn Nine Nine season 4 episode "The Fugitive Part 1". He is in the vicinity of a prisoner breakout, though he did not actually see the crime and spends all screen time enthusiastically answering questions and discussing his pico de gallo. In May 2019, Lynch was cast in the third season of the HBO drama Westworld, set to air in 2020.
Lynch returned to the NFL during the final week of the 2019 regular season, signing with the Seahawks alongside former teammate Robert Turbin on December 23, 2019, after Seattle lost three running backs to injury. Lynch made his debut with the Seahawks in Week 17 against the San Francisco 49ers on NBC Sunday Night Football. During the game, Lynch rushed 12 times for 34 yards and a touchdown in the 26–21 loss. During the Seahawks' 17–9 win over the Philadelphia Eagles in the Wild Card Round of the playoffs, Lynch broke a tackle to score a five-yard, first half touchdown. In the Divisional Round against the Green Bay Packers, Lynch rushed 12 times for 26 yards and two touchdowns during the 28–23 loss.
On March 1, 2020, Lynch is set to appear as a concerned boss of his own sports bar, enlisting the help of Jon Taffer to begin season 7 of Bar Rescue.