The 75th Indianapolis 500 was held at the Indianapolis Motor Speedway in Speedway, Indiana, on Sunday, May 26, 1991. Rick Mears won from the pole position, becoming the third four-time winner of the Indy 500, joining A. J. Foyt and Al Unser. During time trials, Mears also established an Indy record by winning his sixth career pole position. The month of May for Mears was tumultuous, as he suffered his first ever crash at Indy since arriving as a rookie in 1977. The wreck during a practice run totaled his primary car, and injured his right foot. Mears later admitted that pain he was experiencing during the race was so bad, he had to cross his legs in the car and push the accelerator pedal down with his left foot.

The race was noteworthy in that it featured the first African American driver to qualify for the Indy 500, Willy T. Ribbs. It also saw its first Japanese driver, Hiro Matsushita. The pre-race attention going into the month focused on A. J. Foyt, who was expected to retire from driving after the event. During time trials, Foyt qualified on the front row, his record 34th consecutive Indy appearance. On race day, however, he dropped out early due to suspension damage. He eventually retracted his retirement plans, and returned one final time in 1992.

For the first time in Indy history, four members of the same family qualified for the same race. Mario, Michael, Jeff, and John Andretti competed together. Michael, Mario and John all finished in the top ten, while Jeff was named the Rookie of the Year. Michael Andretti led most laps and battled Mears for the win in the closing laps, executing a daring pass for the lead on the outside of turn one on lap 187. Mears, however, returned the favor one lap later, and Michael's second-place finish would end up being his career best finish at Indy.

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