The Chip Ganassi Racing driver set a 174.353 mph two-lap average to beat Team Penske’s David Malukas to top spot by one mile per hour.
Malukas could only watch on in disbelief as his 173.244 mph two-lap average was blitzed.
Andretti Global’s Kyle Kirkwood was third ahead of Indianapolis 500 winner Felix Rosenqvist of Meyer Shank Racing.
Scott McLaughlin was fifth for Team Penske ahead of Kiwi compatriots Marcus Armstrong (Meyer Shank Racing) and Scott Dixon (Chip Ganassi Racing).
Andretti Global driver Will Power had an early draw in qualifying and was 21st.
“The team I have around me, it’s incredible,” said Palou.
“Honestly. My car was on rails today. It was incredible.
“It’s a place that I struggle the most so far. Hopefully we can change it tomorrow.
“I knew this morning that our car was super quick. The #10 Honda Honda had a lot of power, but I did not really expect to get the pole here today, honestly.
“It’s just incredible. Super proud. I cannot wait for tomorrow.”
In his four previous visits to Gateway, Palou has never finished higher than fourth but no lower than ninth.
Palou leads the series standings on 327 points ahead of Kirkwood on 265 points.
Monday’s IndyCar race at Gateway gets underway at 11:25am AEST.
Results: IndyCar Series Bommarito Automotive Group 500, Qualifying
| Pos | Num | Driver | Team | Lap 1 | Lap 2 | Time | Speed (mph) |
| 1 | 10 | Alex Palou | Chip Ganassi Racing | 25.7195 | 25.9000 | 51.6195 | 174.353 |
| 2 | 12 | David Malukas | Team Penske | 25.9024 | 26.0476 | 51.9500 | 173.244 |
| 3 | 27 | Kyle Kirkwood | Andretti Global w/ Curb-Agajanian | 25.9753 | 25.9859 | 51.9612 | 173.206 |
| 4 | 60 | Felix Rosenqvist | Meyer Shank w/ Curb-Agajanian | 25.9592 | 26.0781 | 52.0373 | 172.953 |
| 5 | 3 | Scott McLaughlin | Team Penske | 25.9450 | 26.1175 | 52.0625 | 172.869 |
| 6 | 66 | Marcus Armstrong | Meyer Shank w/ Curb-Agajanian | 26.0724 | 26.1068 | 52.1792 | 172.483 |
| 7 | 9 | Scott Dixon | Chip Ganassi Racing | 26.0340 | 26.1467 | 52.1807 | 172.478 |
| 8 | 2 | Josef Newgarden | Team Penske | 26.0260 | 26.1736 | 52.1996 | 172.415 |
| 9 | 5 | Pato O’Ward | Arrow McLaren | 26.2412 | 26.0868 | 52.3280 | 171.992 |
| 10 | 20 | Alexander Rossi | ECR | 26.1412 | 26.2078 | 52.3490 | 171.923 |
| 11 | 15 | Graham Rahal | Rahal Letterman Lanigan Racing | 26.2634 | 26.2213 | 52.4847 | 171.479 |
| 12 | 28 | Marcus Ericsson | Andretti Global | 26.3296 | 26.1840 | 52.5136 | 171.384 |
| 13 | 76 | Rinus VeeKay | Juncos Hollinger Racing | 26.2721 | 26.2980 | 52.5701 | 171.200 |
| 14 | 8 | Kyffin Simpson | Chip Ganassi Racing | 26.3756 | 26.2103 | 52.5859 | 171.149 |
| 15 | 14 | Santino Ferrucci | A.J. Foyt Enterprises | 26.3731 | 26.2621 | 52.6352 | 170.988 |
| 16 | 7 | Christian Lundgaard | Arrow McLaren | 26.2778 | 26.3672 | 52.6450 | 170.956 |
| 17 | 45 | Louis Foster | Rahal Letterman Lanigan Racing | 26.3437 | 26.4208 | 52.7645 | 170.569 |
| 18 | 47 | Mick Schumacher | Rahal Letterman Lanigan Racing | 26.4258 | 26.4252 | 52.8510 | 170.290 |
| 19 | 21 | Christian Rasmussen | ECR | 26.4473 | 26.4610 | 52.9083 | 170.106 |
| 20 | 4 | Caio Collet | A.J. Foyt Enterprises | 26.4932 | 26.4157 | 52.9089 | 170.104 |
| 21 | 26 | Will Power | Andretti Global | 26.5640 | 26.4802 | 53.0442 | 169.670 |
| 22 | 6 | Nolan Siegel | Arrow McLaren | 26.6388 | 26.5946 | 53.2334 | 169.067 |
| 23 | 18 | Romain Grosjean | Dale Coyne Racing | 26.6362 | 26.6130 | 53.2492 | 169.017 |
| 24 | 19 | Dennis Hauger | Dale Coyne Racing | 26.6890 | 26.6504 | 53.3394 | 168.731 |
| 25 | 77 | Sting Ray Robb | Juncos Hollinger Racing | 26.8616 | 26.6898 | 53.5514 | 168.063 |
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