Dixon debuted in the Championship Auto Racing Teams series in 2001 with PacWest Racing, winning on his third career start at Nazareth Speedway to become the youngest winner of a major open-wheel race at the time. When PacWest folded, Chip Ganassi Racing signed him for the remainder of 2002. Dixon moved with CGR to the IndyCar Series in 2003, winning the championship in his debut season.
He went on to claim IndyCar titles in 2003, 2008, 2013, 2015, 2018, and 2020, accumulating 59 race victories overall. His 2008 season included the Indianapolis 500. In 2015 he tied Juan Pablo Montoya on points but was declared champion on the tiebreak of victories. Dixon has won the Indianapolis 500 once and taken pole there four times. He was named New Zealand's Sportsman of the Year in 2008 and 2013.
Dixon has pursued a parallel endurance racing career alongside IndyCar since 2004. He won the 24 Hours of Daytona three times: in 2006 with CGR, in 2015 with CGR, and in 2020 with Wayne Taylor Racing. He also won the Petit Le Mans twice.
His most prominent sports car chapter came between 2016 and 2019 as an endurance driver for Ford Chip Ganassi Racing. Dixon shared the number 67 Ford GT in the GTLM category of the IMSA WeatherTech SportsCar Championship at the 24 Hours of Daytona, 12 Hours of Sebring, and Petit Le Mans alongside Ryan Briscoe and Richard Westbrook, and competed in the number 69 car at the 24 Hours of Le Mans in the LM GTE-Pro class. The trio's best Le Mans GTE-Pro result was third place in 2016. In 2018 they won the GTLM class at the 24 Hours of Daytona after 783 laps.
For 2020, Dixon switched to the Prototype class at Wayne Taylor Racing, partnering Renger van der Zande as the full-season crew with Kamui Kobayashi joining for the endurance rounds. The number 10 Cadillac DPi-V.R won the 24 Hours of Daytona in January 2020 in a record-breaking 833 laps, with Dixon, van der Zande, Briscoe, and Kobayashi sharing the car. Dixon, van der Zande, and Briscoe also won the Petit Le Mans at Road Atlanta in October 2020. That same year, Dixon claimed his sixth IndyCar championship.
Dixon continued as an endurance driver for Chip Ganassi Racing in IMSA from 2021, moving to the Cadillac DPi-V.R and later the Cadillac V-LHDh GTP car. He achieved a third-place overall finish at the 2023 24 Hours of Daytona and a second-place overall finish at the 2024 Petit Le Mans. From 2025 he drove for Meyer Shank Racing in the IMSA Endurance Cup, finishing second at Daytona.
Dixon was inducted into the Motorsports Hall of Fame of America in March 2024 and the Long Beach Motorsports Walk of Fame in 2025. He has received the Bruce McLaren Trophy, the Jim Clark Trophy four times, and multiple New Zealand sporting awards. He and his wife Emma Davies, a former British 800 metres champion, have three children.