Breadon was also a great baseball fan and, in 1917, he invested $2,000 as a minority owner of the St. Louis Cardinals. He contin ued to buy stock until he had financial control of the team. In 1920, at the request of Branch Rickey, who had been president and field manager, he took over presidency of the club, with Rickey as vice-president. Breadon moved the Cards out of the inadequate wooden Cardinal Park during the 1920 season and into the more modern Sportsman´s Park, owned by the St. Louis Browns.

Early in the 1925 season, with the Cards in last place, Breadon replaced Rickey as field manager with second baseman Rogers Hornsby. That winter Breadon traded the player-manager to the New York Giants for second baseman Frank Frisch and pitcher Jimmy Ring. The trade enraged Cardinal fans, but Frisch ended up being a great player as well.

In 1947 Breadon sold the team to Fred Saigh for several million dollars. During his 30-year tenure, the St. Louis Cardinals won nine pennants and six World Series. He and Branch Rickey were also responsible for setting up baseball´s first farm system for the Cardinals, a move that would be followed later by all other major league teams.[ http://thedeadballera.crosswinds.net/Obits/BreadonSamsObit.html, http://www.pubdim.net/baseballlibrary/ballplayers/B/Breadon_Sam.stm]