SP announced that Oliver Askew, who had driven the No. 7 car in 2020, would not return to the team for the 2021 season. Felix Rosenqvist moved from Chip Ganassi Racing to replace Askew. Askew came back to the No. 7 car for the second race in Detroit, as Rosenqvist was hospitalized after an accident in the weekend's first race. Rosenqvist was then replaced for the next race at Road America by former Formula One and Haas reserve driver Kevin Magnussen after not being medically cleared to drive. Team Penske announced that three-time Supercars champion Scott McLaughlin would race full-time for the team in IndyCar in 2021. Chip Ganassi Racing signed Álex Palou to drive the No. 10 full-time in the 2021 season. After competing in three races in 2020 with both Team Penske and Arrow McLaren SP, Hélio Castroneves contested a six-race schedule in 2021 with Meyer Shank Racing. Chip Ganassi Racing re-signed Tony Kanaan to a two-year contract to contest the oval events, in complement to Jimmie Johnson's road & street course schedule in the No. 48 entry. Kanaan previously drove for the team between 2014 and 2017. Colton Herta switched from the No. 88 Harding Steinbrenner-backed car to the No. 26, sponsored by Gainbridge. Arrow McLaren SP announced that two-time Indianapolis 500 winner Juan Pablo Montoya drove their third entry in the Indianapolis 500. This was Montoya's first Indianapolis 500 appearance since 2017. Montoya also drove the IndyGP. Paretta Autosport, a new team run by former Dodge/SRT Motorsports director Beth Paretta, announced that Simona de Silvestro drove a Team Penske-engineered Chevrolet in the Indianapolis 500. This was de Silvestro's first IndyCar and Indianapolis 500 appearance since 2015. James Hinchcliffe re-joined Andretti Autosport full-time in the No. 29 after competing in 6 races for the team in the 2020 season. Dale Coyne Racing with Vasser-Sullivan signed Ed Jones for the 2021 season. This was Jones' second stint with Dale Coyne Racing, having driven for them in the 2017 season. Dale Coyne Racing with Rick Ware Racing announced that Romain Grosjean would be racing for the team, driving the No. 51 entry on road and street circuits, after 10 seasons in Formula One. Pietro Fittipaldi drove the No. 51 on the ovals. Fittipaldi returned to the IndyCar Series for the first time since 2018. The team later announced that Cody Ware would make his IndyCar debut at Road America