Starting in 1958, Penske purchased, raced and sold race cars, and was very successful both financially and on the track. By 1960, he was a well known race car driver (Sports Illustrated Driver of the Year), winning prestigious races until 1965, when he retired as a driver, to concentrate on the business of owning and running a successful race car team.

His team first competed in the Indianapolis 500 in 1969, winning that event 13 times between 1972 and 2003, and their first NASCAR win was in 1973. His teams have won many races in the subsequent years. He closed his European-based Formula One business in 1977. In 1982, he became the Chairman of the Penske Truck Leasing business.

In 1998, Penske was inducted into the International Motorsports Hall of Fame.

Penske won his first NASCAR Sprint Cup Championship with driver Brad Keselowskir on November 18, 2012.