Sato began karting in Japan at the age of nineteen, winning the national title in 1997. He then moved to Europe with backing from Honda, racing briefly in Vauxhall Junior and Formula Opel before joining the British Formula Three Championship with Carlin Motorsport in 2000. He finished third in the championship that year, winning four races, and dominated the series in 2001, winning twelve of 26 races for the first Japanese driver championship in the British F3.
In 2001, Sato also won two of the most prestigious non-championship Formula Three events of the year: the Masters of Formula Three and the Macau Grand Prix. His Macau victory was a landmark result for Japanese motorsport and confirmed him as a driver of serious international potential, earning him a graduation to Formula One with the Jordan team in 2002 under Honda power.
Sato joined Jordan alongside Giancarlo Fisichella in 2002, showing raw pace but also occasional wildness. He moved to BAR in 2003 as a test driver, replacing Jacques Villeneuve for the Japanese Grand Prix and scoring sixth place. He became a full-time BAR race driver in 2004 and delivered his best Formula One season: qualifying in the top three four times including a front-row start at the European Grand Prix, and scoring a podium at the United States Grand Prix — the first for a Japanese driver since Aguri Suzuki in 1990. He finished eighth in the championship with 34 points, helping BAR finish second in the Constructors' Championship.
After a difficult 2005 season hampered by a team ban following a San Marino Grand Prix disqualification, Sato moved to the new Super Aguri F1 team for 2006, run by his former mentor Aguri Suzuki. The team began with modified older machinery but progressively improved. In 2007, Sato passed Fernando Alonso at the Canadian Grand Prix in a move voted "Overtake of the Year" by F1 Racing magazine and scored the team's first championship point at Barcelona. Super Aguri withdrew from Formula One partway through 2008 due to financial difficulties, ending Sato's Formula One career after four races that season.
Sato returned to racing in the IndyCar Series with KV Racing Technology in 2010. After moving to Rahal Letterman Lanigan Racing for 2012, he made a late-race charge on Dario Franchitti in the Indianapolis 500 — taking a bold move for the lead on the final lap — that earned him lasting appreciation from fans even though he did not win. He signed with A.J. Foyt Enterprises for 2013 and won at Long Beach in his 52nd IndyCar start, becoming the first Japanese driver to win an IndyCar race.
The highlight of his American career came at the 2017 Indianapolis 500, driving for Andretti Autosport. Sato became the first Asian driver to win the race, fulfilling the promise of his aggressive "No Attack, No Chance" philosophy. He returned to Rahal Letterman Lanigan Racing for 2018 and added further wins at Portland and Portland again in 2019, and at Gateway in 2019. On 23 August 2020, he won the Indianapolis 500 for a second time, qualifying from the outside of the front row.
Sato's later career became increasingly part-time. He raced for Dale Coyne Racing in 2022 and joined Chip Ganassi Racing for oval rounds only in 2023 before returning to Rahal Letterman Lanigan for Indianapolis 500-only campaigns from 2024.
Sato is renowned across motorsport for an aggressive, attacking style encapsulated by his motto "No Attack, No Chance." In Formula One he was regarded as one of the fastest drivers of his era over a single lap but prone to incidents under pressure. In IndyCar the same aggression proved decisive, particularly at Indianapolis, where his willingness to commit to bold moves in the closing laps produced two victories.
In 2024 Sato was inducted into the Long Beach Motorsports Walk of Fame. His two Indianapolis 500 victories remain the only wins by an Asian driver in the event's history, making him one of the most significant figures in the internationalization of American open-wheel racing.