The 35th International 500-Mile Sweepstakes was held at the Indianapolis Motor Speedway on Wednesday, May 30, 1951. The event was part of the 1951 AAA National Championship Trail, and was included in the 1951 World Drivers Championship. For the second year in a row, no European Formula One-based teams entered the race.

Duke Nalon, who had suffered serious burns in a crash in 1949, and who missed the 1950 race, made a comeback at Indy by winning the pole position in a Novi.

Heavy attrition saw only eight cars running at the finish. Winner Lee Wallard's car lost its brakes, suffered a damaged exhaust pipe, and broke a shock absorber mounting. In addition to the unbearably uncomfortable ride, Wallard had worn a fire retardant outfit, created by dipping his uniform in a mixture of borax crystals and water. Due to not wearing an undershirt, Wallard suffered serious chafing, and required treatment at the infield hospital after the victory lane celebration. It was estimated he lost 15 pounds during the race.

Wallard's winning car had the smallest displacement in the field. About a week after winning the race, Wallard suffered severe burns in a crash at Reading, which effectively ended his professional racing career.

Three-time winner Mauri Rose, in his 15th Indy start, crashed and flipped on lap 126. It was his final 500, as he retired from driving after the crash.

Time trials was scheduled for six days. Rain, however, pushed qualifying into a seventh day.

The race was carried live on the radio through a network arrangement set up by 1070 WIBC-AM of Indianapolis. Mutual, which had carried the race for several years, had raised its advertising rates for 1951, and lost its primary sponsor for the event, Perfect Circle Piston Rings. As a result, Mutual dropped the coverage altogether. Local station WIBC stepped in to cover the race, and provided its feed to various Mutual affiliates. A total of 26 stations carried the broadcast.

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