Palou clocked a 1:43.1709s on his final lap of the session, having switched to ‘red’ alternate tyres on his #10 Honda.
That left the two-time IndyCar champion, who won at Road America on the way to each of those titles, on top by a margin of 0.0797s over Colton Herta.
The Andretti Global driver had held sway for much of the session thanks to his exploits on the ‘black’ primary tyres and ended up second on a 1:43.2506s in the #26 Honda.
AJ Foyt Racing’s Santino Ferrucci was first of the Chevrolet contingent with a 1:43.1618s in Car #14 which left hm third all-told, ahead of Team Penske’s Josef Newgarden (#2 Chevrolet) on a 1:43.3812s.
Christian Lundgaard (#45 Rahal Letterman Lanigan Racing Honda) took fifth, from series leader Scott Dixon (#9 CGR Honda), Will Power (#12 Penske Chevrolet), Scott McLaughlin (#3 Penske Chevrolet), Pato O’Ward (#5 McLaren Chevrolet), and Marcus Armstrong (#11 CGR Honda).
Romain Grosjean ended up last in the 27-car field after an early crash at Turn 14 in the #77 Juncos Hollinger Racing Chevrolet.
Lundgaard, Power, and Dixon also had offs during the session.
Results: Practice 1
| Pos | Num | Driver | C/E/T | Fastest lap | Split 1st/prev | Lap |
| 1 | 10 | Alex Palou | D/H/F | 1:43.1709 | 16/16 | |
| 2 | 26 | Colton Herta | D/H/F | 1:43.2506 | 0.0797/0.0797 | 11/13 |
| 3 | 14 | Santino Ferrucci | D/C/F | 1:43.3618 | 0.1909/0.1112 | 16/16 |
| 4 | 2 | Josef Newgarden | D/C/F | 1:43.3812 | 0.2103/0.0194 | 6/13 |
| 5 | 45 | Christian Lundgaard | D/H/F | 1:43.3984 | 0.2275/0.0172 | 14/19 |
| 6 | 9 | Scott Dixon | D/H/F | 1:43.5340 | 0.3631/0.1356 | 15/15 |
| 7 | 12 | Will Power | D/C/F | 1:43.5729 | 0.4020/0.0389 | 12/16 |
| 8 | 3 | Scott McLaughlin | D/C/F | 1:43.6215 | 0.4506/0.0486 | 16/17 |
| 9 | 5 | Pato O’Ward | D/C/F | 1:43.6815 | 0.5106/0.0600 | 13/14 |
| 10 | 11 | Marcus Armstrong | D/H/F | 1:43.6957 | 0.5248/0.0142 | 17/18 |
| 11 | 30 | Pietro Fittipaldi | D/H/F | 1:43.7134 | 0.5425/0.0177 | 24/29 |
| 12 | 60 | Felix Rosenqvist | D/H/F | 1:43.7418 | 0.5709/0.0284 | 12/13 |
| 13 | 27 | Kyle Kirkwood | D/H/F | 1:43.7758 | 0.6049/0.0340 | 16/16 |
| 14 | 21 | Rinus VeeKay | D/C/F | 1:43.8637 | 0.6928/0.0879 | 21/22 |
| 15 | 7 | Alexander Rossi | D/C/F | 1:43.9887 | 0.8178/0.1250 | 14/15 |
| 16 | 15 | Graham Rahal | D/H/F | 1:44.0668 | 0.8959/0.0781 | 18/19 |
| 17 | 51 | Luca Ghiotto | D/H/F | 1:44.1009 | 0.9300/0.0341 | 17/22 |
| 18 | 6 | Theo Pourchaire | D/C/F | 1:44.2568 | 1.0859/0.1559 | 19/23 |
| 19 | 28 | Marcus Ericsson | D/H/F | 1:44.3535 | 1.1826/0.0967 | 15/18 |
| 20 | 4 | Kyffin Simpson | D/H/F | 1:44.4443 | 1.2734/0.0908 | 22/24 |
| 21 | 66 | Helio Castroneves | D/H/F | 1:44.5616 | 1.3907/0.1173 | 16/17 |
| 22 | 8 | Linus Lundqvist | D/H/F | 1:44.6000 | 1.4291/0.0384 | 22/24 |
| 23 | 20 | Christian Rasmussen | D/C/F | 1:44.6976 | 1.5267/0.0976 | 19/25 |
| 24 | 41 | Sting Ray Robb | D/C/F | 1:44.9410 | 1.7701/0.2434 | 17/18 |
| 25 | 18 | Jack Harvey | D/H/F | 1:44.9660 | 1.7951/0.0250 | 15/17 |
| 26 | 78 | Nolan Siegel | D/C/F | 1:45.1027 | 1.9318/0.1367 | 17/18 |
| 27 | 77 | Romain Grosjean | D/C/F | 16:48.8117 | 15:05.6408/15:03.7090 | 1/1 |
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