Jim Clark, who finished second the previous year, won the pole position in the Lotus 34 quad-cam Ford V-8. He took the lead at the start, and led for a total of 14 laps. However, a tire failure caused a broken suspension, and he dropped out on lap 47. Team manager Colin Chapman had chosen special soft-compound Dunlop tires for qualifying, and the rules dictated that the same type of tires be used for the race, where they suffered from a high wear rate. Clark's Lotus teammate Dan Gurney was later pulled from the race after experiencing similar tire wear.
Bobby Marshman led during the early stages of the race, at one point stretching his lead to as much as 90 seconds. During his aggressive charge in front, he became uncharacteristically obsessed with putting A. J. Foyt a lap down. On lap 39, he went too low in turn one, bottoming out the car, and dropped out with a broken transmission oil plug. Parnelli Jones later dropped out after a pit fire. With Marshman, Clark, and Jones all out of the race, A. J. Foyt cruised to victory, leading the final 146 laps.
Race winner Foyt drove the whole 500 miles without changing tires. Goodyear supplied tires for some entries, but participated only in practice. No cars used Goodyear tires during the race itself. Foyt's 1964 winning car remains the only car in the collection of the Indianapolis Motor Speedway Hall of Fame and Museum, regularly on display, that has never been restored to pre race condition.
Time trials were scheduled for four days.
Dave MacDonald was driving a car owned and designed by Mickey Thompson, the #83 Sears-Allstate Special. It was a rear-engined car that first raced in 1963, updated with a streamlined body for 1964. The car utilized Allstate tires, manufactured by Armstrong Tire and Rubber Co. Due to rule changes by USAC for 1964, the car was required to utilize 15-inch tires (it previously used 12-inch tires). The wheels were most notably enclosed in the front and the rear by streamlined bodywork, intended to take advantage of aerodynamic effects to increase top speeds. However, it is believed that the wheel encasements, as well as the bodywork in general, made the car difficult to handle.