Buemi began in karting before entering German Formula BMW in 2004, finishing third in his debut year and second in 2005, also taking runner-up at the FBMW World Final. He moved into the Formula Three Euroseries in 2006, finishing 12th in his first full season, then improved to second in 2007 behind Romain Grosjean. His single-seater progression continued in GP2, where he raced for ART Grand Prix and then Arden International. His most memorable GP2 performance came in the 2008 French sprint race, when he started 21st on slick tyres on a drying track and converted the chaotic conditions into a race win.
Buemi was confirmed as a Toro Rosso race driver on 9 January 2009, becoming the first Swiss Formula One race entrant since Jean-Denis Délétraz at the 1995 European Grand Prix. He scored a point on his debut at the Australian Grand Prix — finishing eighth and then promoted to seventh following Lewis Hamilton's disqualification — and added further points in China and Brazil to end the season 16th with six points, the best rookie result of that year's class.
The 2010 season brought one of the most dramatic incidents of his F1 career: at the Chinese Grand Prix, a front suspension wishbone failed while he was travelling at over 300 km/h, launching both front wheels off the car. One wheel cleared the safety fence and landed near spectators; Buemi continued into the barriers but escaped injury. He finished the year with eight points, ahead of teammate Jaime Alguersuari's five.
On 14 December 2011, Toro Rosso announced that both Buemi and Alguersuari had been dropped in favour of Daniel Ricciardo and Jean-Éric Vergne. Buemi moved into a test and reserve driver role with Red Bull Racing from 2012, a relationship he maintained for several years.
Buemi joined Toyota Motorsport's Le Mans programme in 2012. In 2014, driving the Toyota TS040 Hybrid alongside Anthony Davidson, he claimed the FIA World Endurance Championship drivers' title with four wins from eight races. He added the 2018–19 WEC title after winning the 2018 24 Hours of Le Mans, then repeated at Le Mans in 2019, 2020, and 2022. His four Le Mans victories equal a record shared with a small number of drivers in the modern era, and his loyalty to Toyota — competing with the same manufacturer without interruption from 2012 onward — is unmatched in the current WEC grid. He and Brendon Hartley are tied for the most FIA WEC titles, each holding four.
Buemi was one of the founding competitors of the Formula E championship, joining e.dams alongside Nicolas Prost for the inaugural 2014–15 season. He finished second in that first championship, one point behind Nelson Piquet Jr., having won in Monaco and London from pole position.
Season two, 2015–16, saw Buemi dominate the early rounds. The championship finale in London descended into drama when title rival Lucas di Grassi drove into Buemi at the first corner of the deciding race. The championship was resolved by fastest lap: Buemi needed to secure it in his second car while di Grassi had to do the same. Buemi delivered under pressure to claim the 2015–16 Formula E title.
Season three opened with three consecutive victories — a first in the championship's history — and Buemi appeared on course to defend his title before skipping the New York double-header to fulfil his WEC commitments. Combined with two disqualifications for technical infringements, the absence cost him the championship to di Grassi at the final race.
His subsequent seasons with Nissan e.dams (from 2018–19) were more volatile. A run of retirements and penalties early in 2018–19 was reversed by a win in New York and a second-place championship finish. He later moved to Envision Racing from 2022–23, continuing to compete at the front of the field.
Buemi ranks among the all-time leading winners in Formula E history, tied with António Félix da Costa for second place behind Mitch Evans.
Buemi is from Aigle in the Swiss canton of Vaud and has resided in Monaco and Switzerland across his career. He married Jennifer in 2015; the couple have three sons. His grandfather Georges Gachnang and first cousin Natacha Gachnang are also racing drivers. In 2013, Buemi and Johnny Herbert mentored six contestants in an ITV4 reality series that aimed to take Gran Turismo video game players to the Dubai 24 Hour race as real competitors.