For 1991, Team Penske welcomed a new title sponsor, Marlboro, and reduced its driver lineup to two with Mears and Fittipaldi. Mears started the CART series season strong, finishing no lower than fifth in the first three races.

However, during the final Indianapolis 500 practice day before "Pole Day" qualifications, a loose nut in Mears' rear suspension caused a failure in Turn 1, resulting in a severe crash. It was the first time Mears crashed at Indianapolis in 14 years of “500” competition. Mears suffered fractures in his right foot, but he was back on track in his backup car in less than three hours. On "Pole Day," Mears set a four-lap average of 224.113 mph and captured his sixth “500” pole position. The Front Row was arguably the greatest ever, with Mears joined by A.J. Foyt and Mario Andretti.

At the start of the race, Mears took the lead in Turn 1. While battling the pain from his days-old foot fractures, Mears realized that he could lower the pain if he used his left foot over his right. The 75th Indianapolis 500 is remembered for the late-race duel between Mears and Michael Andretti. The green flag flew after a caution with 13 laps to go, and Andretti used lapped cars to pass Mears on the outside entering Turn 1—a move that stunned the crowd. Mears made the same daring outside move on Andretti in Turn 1 on the next lap, however—one of the most iconic passes in Indianapolis 500 history. Mears led the final 12 laps to clinch his fourth Indianapolis 500 victory, a feat only accomplished by Foyt and Al Unser before him and no one else for 30 years.