The St. Louis Cardinals (NFL) played their first game at Busch Stadium on September 11, 1966 against the Philadelphia Eagles. Three tiers of 50,000 red circled the grass field. In order for the stadium to be converted from a baseball field to football, two sets of 8,000 seats could be moved parallel to each other to form the football gridiron. Astroturf replaced natural grass in 1973 so the stadium could be converted easily from football to baseball. By the mid 1980s the Cardinals were struggling on the field and attracting fans to Busch Stadium. They were also unsuccessful in trying to get a new football stadium built for the team. After the 1987 the Cardinals moved to Phoenix and Sun Devil Stadium. The St. Louis Cardinals played their last game at Busch Stadium on December 13, 1987 against the New York Giants.

The St. Louis Cardinals (MLB), were the only tenant at the stadium until 1995, when the Los Angeles Rams moved to St. Louis. The Rams played part of the 1995 season at Busch Stadium and then moved into their own stadium, the Edward Jones Dome. The last football game ever at Busch Stadium was played on October 22, 1995 against the San Francisco 49ers. After the Rams left Busch Stadium, it was retrofitted for baseball only. Grass replaced the Astroturf and numerous other improvements were completed at Busch Stadium. The St. Louis Cardinals (MLB) played at Busch Stadium until October 2005 and will move into a new ballpark in April 2006. Busch Stadium was demolished in November 2005.