7 Up was created by Charles Leiper Grigg, who launched his St. Louis–based company The Howdy Corporation in 1920. Grigg came up with the formula for a lemon-lime soft drink in 1929. The product, originally named "Bib-Label Lithiated Lemon-Lime Soda", was launched two weeks before the Wall Street Crash of 1929. It contained lithium citrate, a mood-stabilizing drug, until 1948. It was one of a number of patent medicine products popular in the late-19th and early-20th centuries. Its name was later shortened to "7 Up Lithiated Lemon Soda" before being further shortened to just "7 Up" by 1936.
7 Up has been reformulated several times since its launch in 1929. In 2006, the version of the product sold in the U.S. was reformulated so it could be marketed as being "100% natural". This was achieved by eliminating the chelating agent calcium disodium EDTA, and replacing sodium citrate with potassium citrate to reduce the beverage's sodium content. This reformulation contains no fruit juice and, in the U.S., is sweetened with high-fructose corn syrup (HFCS). The manufacturing process used in the production of HFCS has led some public health and advocacy groups to challenge the ad campaign's "natural" claims.
In 1974, 7 Up became The Jerry Lewis MDA Labor Day Telethon's first corporate sponsor; this was at a time when its sponsorship was generally limited to trade unions and civic organizations.
The 7 Up company was privately owned by its founding families until it was sold in 1978 to Philip Morris, which sold it in 1986 in two parts: the international division to PepsiCo and the US business to a group led by the investment firm Hicks & Haas. In the US, 7 Up merged with Dr Pepper in 1988; Cadbury Schweppes bought the combined company in 1995. The Dr Pepper Snapple Group was spun off from Cadbury Schweppes in 2008; it merged with Keurig Green Mountain in 2018 to form Keurig Dr Pepper.
In 1987, 7 Up introduced Spot, the red-orange dot in the 7 Up logo anthropomorphized into a mascot. The character was used heavily in advertising and licensed items across the U.S., including the 1993 platform video game Cool Spot.
In 1991, 7 Up sponsored Jordan Grand Prix's Jordan 191, the car in which Michael Schumacher drove his first Formula One race.
In 2007, Cadbury Schweppes entered into a licensing partnership with Vita Food Products to produce a line of barbecue sauces and marinades flavored with Dr Pepper, 7 Up, and A&W Root Beer.
In 2007, after the Center for Science in the Public Interest threatened to sue 7 Up, it was announced that 7 Up would stop being marketed as "100% natural". Instead, it is now promoted as having "100% Natural Flavors". The controversy does not extend to other countries, such as the United Kingdom, where HFCS is not generally used in foods, including 7 Up. In 2011, 7 Up began test marketing a formula, called 7 Up Retro, using sugar rather than HFCS. Container labels sport the caption "Made With Real Sugar".
As with the regular variety, it was reformulated as Diet Cherry 7 Up Antioxidant in 2009 before reverting to the original formula in 2013. It was rebranded as Cherry 7 Up Zero Sugar in late 2020.
It was renamed and reformulated as Cherry 7 Up Antioxidant in January 2009; however, the soda's antioxidant line was pulled from shelves in 2012 amid a controversy about the rumored detrimental health effects of consuming antioxidant drinks, and the original formula returned.
Tropical 7UP was rereleased again in 2023 at Kroger-owned stores.
Diet 7 Up was later reformulated and advertised as being sweetened with sucralose and Acesulfame Potassium replacing Aspartame. The recipe later reverted to using Aspartame. The beverage was rebranded as 7 Up Zero Sugar in late 2020.