The 21st International 500-Mile Sweepstakes Race was held at the Indianapolis Motor Speedway on Tuesday, May 30, 1933. Louis Meyer defeated Wilbur Shaw by a time of 401.89 seconds (6.69 minutes). The average speed of the race was 104.162 miles per hour (167.632 km/h) while Bill Cummings achieved the pole position with a speed of 118.521 miles per hour (190.741 km/h). The race was part of the 1933 AAA Championship Car season.

Meyer was accompanied by riding mechanic Lawson Harris.

The 1933 month of May at Indianapolis would go on record as the deadliest running of the 500. Five participants were fatally injured. During practice, Bill Denver and his riding mechanic Bob Hurst were killed in a crash. On race day, Mark Billman was killed in a crash on lap 79 while Lester Spangler and his riding mechanic G.L. "Monk" Jordan were killed in a crash on lap 132. It was the fifth straight year at least one competitor would die in a crash during the month.

Ten-lap (25 mile) qualifying runs were utilized.

For 1933, riding mechanics were required.

In 1933, one of the more famous bits of Indy 500 nostalgia occurred. Telegraph was still being used to transmit race information to newspapers and other outlets across the United States. George Zanaon, a typesetter for The World-Independent newspaper in the town of Walsenburg, Colorado was preparing a story for that day's Indianapolis 500. Since Memorial Day was a holiday, his young editor John B. Kirkpatrick was alone monitoring the Associated Press wire for race updates. The race took several hours to complete, and the AP wire was shut down prior to the finish. Fitzpatrick had nearly the entire story ready for print, minus the winner of the race. A helpful AP editor in Denver advised him that he would send the name of the winner via Western Union telegraph.

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