Isaiah Hartenstein was born on May 5, 1998.
In 2008, Isaiah Hartenstein and his family moved to Germany, where his father pursued a professional basketball career.
Isaiah Hartenstein joined the youth ranks of MTV Gießen in 2009 and later the QTSV Quakenbrück/Artland Dragons, following his father's signing with the Artland Dragons.
During the 2013-14 season, Isaiah Hartenstein led the Artland Dragons' junior team to a German championship in the Under-16 Bundesliga JBBL, earning the Most Valuable Player award. He averaged 20.9 points, 12.1 rebounds, 3.4 assists, 2.9 steals, and 1.9 blocks throughout the season. Notably, his father, Florian, served as the team's head coach and received the JBBL Coach of the Year award.
Isaiah Hartenstein represented Germany at the 2014 FIBA Europe Under-16 Championship.
Isaiah Hartenstein was selected to play in the 2014 Jordan Brand Classic International Game, where he scored four points and grabbed five rebounds in 18 minutes of play.
Isaiah Hartenstein made his debut in Germany's top-tier level Basketball Bundesliga on February 1, 2015, playing for 1 minute and 12 seconds against Eisbären Bremerhaven.
In August 2015, Isaiah Hartenstein signed a deal with Lithuanian powerhouse Žalgiris Kaunas but remained with the Artland Dragons on loan. The Dragons had been relegated to the 2. Bundesliga ProB, Germany's third division. During the 2015-16 campaign, Hartenstein played 14 games for the Quakenbrück based side, averaging 11.6 points, 8.9 rebounds, 2.1 blocks, 1.6 steals, and 1.4 assists.
Isaiah Hartenstein represented Germany at the 2015 FIBA Europe Under-18 Championship.
In January 2016, Isaiah Hartenstein decided to leave the Artland Dragons and join Žalgiris Kaunas.
Isaiah Hartenstein participated in the "Basketball Without Borders Global Camp" during the NBA All-Star Weekend in Toronto, Canada, in February 2016.
On September 28, 2016, Isaiah Hartenstein debuted for Žalgiris in Lithuania's top-flight league, the LKL, against Šiauliai. He also played in the EuroLeague against Fenerbahce on October 26. Later that season, he contributed to Žalgiris' first-ever King Mindaugas Cup victory.
Isaiah Hartenstein played a key role in Germany's fourth-place finish at the 2016 FIBA Europe Under-18 Championship. He led the team with averages of 14.7 points, 9.5 rebounds, 1.7 blocks, and 1.7 steals per game, earning him a spot on the tournament's "All-Star Five."
Isaiah Hartenstein delivered an impressive performance at the Nike Hoop Summit on April 7, 2017, scoring 10 points and securing three rebounds in 19 minutes of play.
Isaiah Hartenstein declared for the 2017 NBA draft on April 22, 2017. Although invited to the 2017 NBA Draft Combine, he chose not to participate.
Isaiah Hartenstein was drafted by the Houston Rockets as the 43rd overall pick in the 2017 NBA draft on June 22, 2017. Subsequently, he participated in the 2017 NBA Summer League with the team.
Isaiah Hartenstein debuted for the German men's national team in August 2017 and participated in EuroBasket 2017, where he averaged 4.3 points and 2.5 rebounds per game.
During the 2017-18 season, Isaiah Hartenstein played 38 games in the NBA G League, representing the Rio Grande Valley Vipers. He averaged 9.5 points and 6.6 rebounds per game.
The Houston Rockets signed Isaiah Hartenstein on July 25, 2018.
Isaiah Hartenstein played a crucial role in the Rio Grande Valley Vipers' victory in the 2018-19 NBA G League championship. In the series-clinching game, he scored 33 points and made a career-high 8 three-pointers, earning him the NBA G League Finals MVP award.
Isaiah Hartenstein achieved his first career triple-double on February 7, 2019, recording 12 points, 16 rebounds, and 11 assists in a 103-102 road win against the Salt Lake City Stars.
Isaiah Hartenstein was suspended without pay for one game after leaving the bench during an altercation in a game against the Memphis Hustle on December 17, 2019. The Rio Grande Valley Vipers lost the game 132-109.
On June 23, 2020, the Houston Rockets announced that they had waived Isaiah Hartenstein.
The Denver Nuggets announced the signing of Isaiah Hartenstein to a multi-year contract on November 30, 2020. Playing as a backup to All-Star center Nikola Jokic, Hartenstein averaged 9 minutes, 3.5 points, and 2.8 rebounds per game.
In a trade involving center JaVale McGee, Isaiah Hartenstein and two future second-round picks were traded to the Cleveland Cavaliers on March 25, 2021. In his first twelve games with the Cavs, Hartenstein averaged 19 minutes of playing time, contributing 9 points, 7 rebounds, 2.6 assists, and 1.4 blocks per game.
Isaiah Hartenstein signed with the Los Angeles Clippers on September 27, 2021.
Isaiah Hartenstein signed a two-year, $16 million contract with the New York Knicks on July 12, 2022.