Scott Dixon (Chip Ganassi Racing) entered his 21st season competing for a National Championship as the defending champion, but ultimately finished the campaign in fourth place.

[2] Third place in the championship went to Pato O'Ward for Arrow McLaren SP, who like Newgarden, won two races during the season.

[79] On January 6, 2021, the Firestone Grand Prix of St. Petersburg was rescheduled to April 25 because of the COVID-19 pandemic, with the season opener being moved to Barber Motorsports Park.

[80] On January 22, 2021, the Honda Indy Grand Prix of Alabama was rescheduled to April 18 because of the COVID-19 pandemic and was now on NBC network television.

[81] On May 14, 2021, the Honda Indy Toronto was cancelled for a second successive season, due to the restrictions imposed in Ontario because of the COVID-19 pandemic.