Despite the long hours of practice, there were no accidents, and a combined total of 3,450 laps were completed.

The fastest lap of the day, 39.2261 seconds, was set just after 4：30 pm by two-time Indy 500 winner Takuma Sato (Chip Ganassi Racing, 2017 and 2020). Sato, making his 14th appearance this year, secured his seat with Chip Ganassi Racing, last year's Indy 500-winning team, and put on a thrilling performance from the first practice session. Sato completed 92 laps on four sets of tires, steadily working on his car settings. On his 78th lap, he set the fastest lap of the day. His teammates also had an impressive day. Scott Dixon, pole-sitter for the last two years, was second-fastest with a 229.174 mph average. Alex Palou was fourth-fastest with an average speed of 228.720 mph. Defending champion Marcus Erickson was seventh with 227.701 mph.

Colton Herta (Andretti-Herta Autosport with Curb-Agajanian) was sixth-fastest and Marco Andretti (Andretti-Herta Autosport with Marco and Curb-Agajanian) was tenth for the day. Honda teams not only dominated the top two positions, but also placed 6 drivers in the top ten, making for a great start to the month of May.