Indy 500 polesitter Alex Palou is out of contention following a crash in the pits during the first caution of the race.
The race had run 91 laps under green-flag conditions in a remarkably clean opening, with Arrow McLaren duo Felix Rosenqvist and Patricio O'Ward at the front of the field.
But approaching the end of the third tyre stint, Dale Coyne Racing driver Sting Ray Robb got into the marbles at Turn 1 avoiding Graham Rahal, who had taken the initiative to the inside.
Robb was powerless to stop his car from sliding up into the wall, bringing his day to an end.
In the ensuing yellow-flag pit stops, Ed Carpenter Racing driver Rinus Veekay spun when exiting his pit stall and swiped into Palou, having battled for the lead throughout the opening quarter of the race.
Chip Ganassi Racing driver Palou was wheeled back to his pit stall with the team attempting to repair the car and get the Spaniard back on track, though his chances of winning are gone.
With 97 laps gone, Callum Ilott pitted before the caution and has cycled to the front, with Rosenqvist and O'Ward behind.