Ferrucci competed in German Formula Three with EuroInternational, scoring a second place in his fourth race, and also raced in British Formula 3 with Fortec Motorsport, winning two races and taking a pole. He moved to the GP3 Series with DAMS for 2016, finishing twelfth overall, then transitioned to the FIA Formula 2 Championship with Trident mid-season in 2017, managing ninth as his best result.
For the 2018 FIA Formula 2 season Ferrucci remained at Trident. In July 2018, at Silverstone, he was found to have made deliberate contact with teammate Arjun Maini following the sprint race, and separately forced Maini off the track during the race itself. The FIA banned him from four F2 rounds and fined him €60,000. An attempt to display a "Make America Great Again" livery on his car was blocked as a violation of the FIA's political slogans policy. He was subsequently dismissed by Trident, who later cited non-payment of contractual fees; an Italian court later ordered Ferrucci to pay Trident €502,000 plus interest.
Ferrucci had also served as a test and development driver for the Haas F1 Team in 2016, 2017, and 2018, receiving his first taste of Formula One machinery at a Silverstone test after the 2016 British Grand Prix.
Ferrucci debuted in IndyCar in June 2018 with Dale Coyne Racing at the Detroit Grand Prix as a substitute for Pietro Fittipaldi, retiring after contact from Charlie Kimball. He contested the final two rounds of 2018 with Coyne after leaving Formula 2.
In 2019 Ferrucci signed a full IndyCar season with Dale Coyne Racing. He scored top-ten finishes in his first two races before achieving Indy 500 Rookie of the Year honours, moving from 23rd on the grid to seventh at the finish. Three races later he produced his best IndyCar result to that point with fourth at Texas Motor Speedway.
The 2020 season was his strongest at Coyne: he finished fourth at the Indianapolis 500 and scored five top-fives across fourteen starts, ending thirteenth in the championship.
After a part-time 2021 with Rahal Letterman Lanigan Racing — where he qualified and finished sixth at the Indianapolis 500, the best Rahal result of the race — and scattered appearances in 2022, Ferrucci joined A.J. Foyt Racing full-time for 2023 alongside IndyCar rookie Benjamin Pedersen.
His 2023 Indianapolis 500 was the highlight: qualifying fourth at 233.661 mph, he drove to third place at the finish, the best result for an A.J. Foyt Racing entry since 2000. He continued with Foyt in 2024 alongside Sting Ray Robb, qualifying sixth for the Indy 500 and finishing eighth. His season was the team's best in years, delivering eleven top-ten finishes from seventeen starts and a ninth-place championship finish, helped by the team's new technical partnership with Penske. He also took his first IndyCar pole position at Portland before finishing eighth in that race.
In 2025 Ferrucci continued his upward trajectory. He finished fifth at the Indianapolis 500 and then strung together four consecutive top-five results, including his second and third career podiums at Detroit and Road America.
In 2021 Ferrucci ran twenty races in the NASCAR Xfinity Series for Sam Hunt Racing in the No. 26 Toyota Supra, his first serious stock car campaign. He made additional Xfinity appearances at Pocono and the Indianapolis Road Course in 2022 with the same team.