Uematsu was born in Kōchi, Kōchi Prefecture, Japan. A self-taught musician, he began to play the piano when he was between the ages of eleven and twelve years old, and he did not take any formal piano lessons. He has an older sister who also played the piano. After graduating from Kanagawa University with a degree in English, Uematsu played the keyboard in several amateur bands and composed music for television commercials. When Uematsu was working at a music rental shop in Tokyo, a Square employee asked if he would be interested in creating music for some of the titles they were working on. Although he agreed, Uematsu at the time considered it a side job, and he did not think it would become a full-time career. He said it was a way to make some money on the side, while also keeping his part-time job at the music rental shop.
Uematsu joined Square in 1985, and composed the soundtrack to Cruise Chaser Blassty in 1986, his first. While working at Square, he met Hironobu Sakaguchi, who asked him if he wanted to create music for some of his games, which Uematsu agreed to. For the next year, he created music for a number of games which did not achieve widespread success, including titles like Genesis and Alpha. In 1987, Uematsu and Sakaguchi collaborated on what was originally to be Sakaguchi's last contribution for Square, Final Fantasy, a game that turned out to be a huge success.
Final Fantasy's popularity sparked Uematsu's career in video game music, and he would go on to compose music for over 30 titles, most prominently the subsequent games in the Final Fantasy series. He scored the first installment in the SaGa series, The Final Fantasy Legend, in 1989. For the second game in the series, Final Fantasy Legend II he was assisted by Kenji Ito. In late 1994, Uematsu signed on to finish the soundtrack for the critically acclaimed title Chrono Trigger after the game's composer, Yasunori Mitsuda, contracted peptic ulcers. In 1996, he co-composed the soundtrack to Front Mission: Gun Hazard, and created the entire score for DynamiTracer. He also created music for three of the games in the Hanjuku Hero series.
Outside video games, he has composed the main theme for the 2000 animated film Ah! My Goddess: The Movie and co-composed the anime Final Fantasy: Unlimited (2001) with Final Fantasy orchestrator Shirō Hamaguchi. He also inspired the Ten Plants concept albums, and released a solo album in 1994, entitled Phantasmagoria. Feeling gradually more dissatisfied and uninspired, Uematsu requested the assistance of composers Masashi Hamauzu and Junya Nakano for the score to Final Fantasy X in 2001. This marked the first time that Uematsu did not compose an entire main-series Final Fantasy soundtrack. For Final Fantasy XI from 2002, he was joined by Naoshi Mizuta, who composed the majority of the soundtrack, and Kumi Tanioka; Uematsu was responsible for only eleven tracks. In 2003, he assisted Hitoshi Sakimoto in scoring Final Fantasy Tactics Advance by providing the main theme.
In 2002, fellow Square colleagues Kenichiro Fukui and Tsuyoshi Sekito asked Uematsu to join them in forming a rock band that focused on reinterpreting and expanding on Uematsu's compositions. He declined their offer at first because he was too busy with work; however, after agreeing to perform with Fukui and Sekito in a live performance as a keyboardist, he decided to join them in making a band. Another employee at Square, Mr. Matsushita, chose the name The Black Mages for their band. In 2003, Keiji Kawamori, Arata Hanyuda, and Michio Okamiya also joined the band. The Black Mages released three studio albums, and appeared at several concerts to promote their albums.
Uematsu left Square Enix in 2004 and formed his own production company, Smile Please. He later founded the music production company and record label Dog Ear Records in 2006. The reason for Uematsu's departure was that the company moved their office from Meguro to Shinjuku, Tokyo, and he was not comfortable with the new location. Also, he cites the fact that he had reached an age where he should gradually take his life into his own hands. He does, however, continue to compose music as a freelancer for Square Enix. In 2005, Uematsu and several members of The Black Mages created the score for the CGI film Final Fantasy VII Advent Children. Uematsu composed only the main theme for Final Fantasy XII (2006); he was originally offered the job of creating the full score, but Sakimoto was eventually assigned as the main composer instead. Uematsu was also initially going to create the theme song for Final Fantasy XIII (2010). However, after being assigned the task of creating the entire score of Final Fantasy XIV, Uematsu decided to hand the job over to the main Final Fantasy XIII composer, Hamauzu.
Uematsu also works closely with Sakaguchi's development studio Mistwalker, and has composed for Blue Dragon (2006), Lost Odyssey (2007), Away: Shuffle Dungeon (2008); The Last Story (2011); and Terra Battle (2014). He also wrote music for the cancelled game Cry On.
Uematsu created the main theme for the multi-composer game Super Smash Bros. Brawl in 2008. He then composed the music for the 2009 anime Guin Saga; this marked the first time he provided a full score for an animated series. Uematsu recently contributed music and storyline to an e-book titled called "Blik-0 1946".
Uematsu appeared five times in the top 20 of the annual Classic FM Hall of Fame. In 2012, "Aerith's Theme", written by Uematsu for Final Fantasy VII, was voted into the number 16 position in the annual Classic FM (UK) "Hall of Fame" top 300 chart. It was the first time that a piece of music written for a video game had appeared in the chart. In 2013, music from the Final Fantasy series received even greater support and was voted into the third position on the Classic FM Hall of Fame. Uematsu and his Final Fantasy music subsequently appeared at number seven in 2014, number nine in 2015, and number 17 in 2016.
In September 2018, Uematsu announced that he would take the remainder of the year off from touring and postponed his projects indefinitely in order to recover from an unspecified illness.
Uematsu currently resides in Tokyo, Japan with his wife, Reiko, whom he met during college, and their beagle, Pao. They have a summer cabin in Yamanakako, Yamanashi. In his spare time, he enjoys watching professional wrestling, drinking beer and bicycling. Uematsu has said he originally wanted to become a professional wrestler, mentioning it was a career dream when he was younger.