University of Detroit Stadium was the home field for the NFL's Detroit Lions from 1934 to 1937, and again in 1940. The Lions also played several early season home games there in 1938 and 1939. The stadium was also home to the Detroit Wolverines for their only NFL season in 1928. U of D stadium was the site of the 1935 NFL Championship Game, won by the Lions over the New York Giants, 26–7.

The Detroit Cougars professional soccer club played several games here in the summers of 1967 and 1968 whenever their regular home field, Tiger Stadium had a scheduling conflict. One such match in 1967 against the Houston Stars ended in an infamous player riot on June 14.

The Michigan Arrows of the fledgling Continental Football League used the stadium (which then had a capacity of 20,000) for the 1968 season. Unfortunately, the Arrows drew just 4,240 fans per game en route to a 1-11 season. The Arrows moved to Midland to become the Tri-City Apollos in 1969, then folded with the rest of the league.

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