Scott Dixon fended off a late charge from Indianapolis 500 winner Takuma Sato at Gateway to record his 50th IndyCar career win and extend his championship points lead.
The five-time series champion's Chip Ganassi machine had jumped long-term leader Patricio O'Ward (Arrow McLaren SP) in the final green-flag pit-stops on lap 162 of 200 to take a net lead, with Sato (Rahal Letterman Laningan) running 13 laps longer than Dixon.
However Sato's right-rear tyre change was slow and an 11-second stop denied him the opportunity to overcut Dixon.
Sato emerged in third place, but the ex-Formula 1 driver quickly passed O'Ward around the outside of Turn 1 with 21 laps remaining and set about closing the two second buffer to Dixon.
With fresher Goodyear tyres and less fuel aboard, Sato soon closed to within 0.3s but was unable to make a move on Dixon, who recorded his fourth win of 2020 and became just the third driver after A.J Foyt (67) and Mario Andretti (52) to reach the landmark of 50 wins in US open wheel racing.
O'Ward, who had undercut poleman Will Power at the first round of pitstops around lap 63, took his second top three result of the season ahead of Colton Herta's Andretti Autosport machine.
After starting fourth, Marcus Ericsson made it two Ganassi finishers in the top five with an effective drive to fifth, his second top five of the campaign.
Rinus Veekay ran off-strategy for a majority of the race, often pitting around 15 laps before the pack, and this brought the Dale Coyne Racing rookie sixth place ahead of Ryan Hunter-Reay (Andretti) and Felix Rosenqvist (Ganassi).
In what is expected to be his final non-Indy 500 weekend in IndyCar, 2004 champion Tony Kanaan scored his best result in over a year by bringing his A.J Foyt Racing entry home in ninth, one place ahead of Carlin's Conor Daly.
Reigning champion Josef Newgarden's race was scuppered by a brief lap 109 caution for weather.
Newgarden and Penske team-mate Power had made their second pitstops in the laps prior to the caution, and did not have time to cycle out before the yellows were flown.
Whilst Power could only finish a twice-lapped 17th after pitting for a puncture on lap 134 and having to make another late stop, Newgarden salvaged a 12th place finish.
Before the race had even started, Alexander Rossi was taken out in a bizarre incident triggered by Alex Palou breaking out of line early just before the start.
Simon Pagenaud had to brake sharply to avoid Palou but was then rammed by McLaren's Oliver Askew and tagged Rossi as he spun.
Rossi's front right clipped the wall, and further contact including team-mates Marco Andretti and Zach Veach eliminated all three, as well as Ed Carpenter - whose Indy 500 was ruined by lap one contact with Veach.
Pagenaud struggled on to lap 67 before he retired with gearbox gremlins.
Results - 200 laps
|1||Scott Dixon||Chip Ganassi Racing||1h44m30.7944s|
|2||Takuma Sato||Rahal Letterman Lanigan||0.1404s|
|3||Patricio O'Ward||Arrow McLaren SP||7.0052s|
|4||Colton Herta||Andretti Harding||7.7019s|
|5||Marcus Ericsson||Chip Ganassi Racing||8.3504s|
|6||Rinus Van Kalmthout||Ed Carpenter Racing||12.4145s|
|7||Ryan Hunter-Reay||Andretti Autosport||13.0556s|
|8||Felix Rosenqvist||Chip Ganassi Racing||13.8107s|
|9||Tony Kanaan||A.J. Foyt Enterprises||15.0319s|
|11||Jack Harvey||Meyer Shank Racing||16.2600s|
|12||Josef Newgarden||Team Penske||16.8155s|
|13||Charlie Kimball||A.J. Foyt Enterprises||21.4079s|
|14||Oliver Askew||Arrow McLaren SP||24.0143s|
|15||Alex Palou||Dale Coyne Racing||24.6954s|
|16||Santino Ferrucci||Dale Coyne Racing with Vasser Sullivan||27.0938s|
|17||Will Power||Team Penske||2 Laps|
|18||Graham Rahal||Rahal Letterman Lanigan||Mechanical|
|19||Simon Pagenaud||Team Penske||Contact|
|20||Ed Carpenter||Ed Carpenter Racing||Contact|
|21||Zach Veach||Andretti Autosport||Contact|
|22||Alexander Rossi||Andretti Autosport||Contact|
|23||Marco Andretti||Andretti Autosport||Contact|