Ferrucci made his Formula 2 debut in Hungary and finished the remainder of the year with Trident, with ninth his best result for a race and 22nd in the season standings.

[5] His attempt to run a "Make America Great Again" livery in support of Donald Trump was blocked by the FIA as being in violation of the political slogans policy.

[6] On July 18, Ferrucci was summarily fired by the Trident F2 team, citing behavioral issues, and non-payment of money required by contract.

Trident alleged that money had been made available for the Detroit IndyCar race, whilst noting that Ferrucci had defaulted on F2 debt to them.

[7][8] An Italian court subsequently ordered Ferrucci to pay Trident €502,000, plus interest and legal fees, for failing to make payments.

[12][13] In June 2018, Ferrucci made his debut in the IndyCar Series at the Detroit Grand Prix for Dale Coyne Racing as a substitute for Pietro Fittipaldi.

After his departure from Formula 2, Ferrucci contested the final two rounds of the IndyCar Series season with Dale Coyne Racing.

In his season debut at the Grand Prix of St. Petersburg, Ferrucci recorded a Top-10 finish, bringing his car home in 9th position.

After qualifying 23rd for the Indy 500, Ferrucci moved through the 33 car field to finish in 7th position, earning him Rookie of the Year honors in his first-ever race at the Indianapolis 500.

Three races later, Ferrucci recorded his best career IndyCar finish by taking the checkered flag in 4th position at Texas Motor Speedway.

Ferrucci signed with Rahal Letterman Lanigan Racing to run a third car sponsored by Hyvee at the 2021 Indianapolis 500.

Ferrucci's results at the Indy 500 earned him four additional drives with RLL at Detroit, Mid Ohio, and Nashville.

RLL ultimately chose Alpine Academy driver Christian Lundgaard to drive their third car full time, ending Ferrucci's tenure with the team.

After Callum Ilott crashed during the 2022 Indianapolis 500 and was deemed not fit by Indycar, Ferrucci was appointed as his replacement at the Detroit Grand Prix.

[20][21] In June, Ferrucci apologized for making homophobic comments after Saturday practice incidents involving Andretti Global drivers Colton Herta and Kyle Kirkwood at the 2024 Detroit Grand Prix.

[24] In January 2021, Ferrucci made his midget car racing debut in the Chili Bowl for Dave Mac Motorsports.