The Stars were a continuation of a franchise originally organized as the St. Louis Giants in 1909 by a white businessman, Charlie Mills. The Giants were a charter member of the Negro National League in 1920, and after two seasons in the league, Mills sold the franchise to Dick Kemp and Dr. Sam Sheppard. Under the new ownership, the name was changed and the ball club became the St. Louis Stars.
In their first year as the Stars, the team finished at an even .500 for the season. In 1923 the Stars experienced a losing season for the only time in their history, while remaining in the Negro National League until its demise following the 1931 season. In 1925 they won the second half title of the split season but lost a seven game series to the Kansas City Monarchs, winners of the first half, 4 games to 3. After this initial setback, the Stars won three pennants, in 1928, 1930, and 1931, winning playoffs the first two seasons against the Chicago American Giants and the Detroit Stars, respectively. Their third flag was the last one in the history of the league that Rube Foster founded and, following the lead of the league itself, the Stars disbanded following the 1931 season.
Six years later, a new franchise bearing the same name became a charter member of the Negro American League, fielding teams in 1937 and 1939. Struggling for financial survival, the franchise shifted to a co-hometown status, pairing St. Louis with other cities-New Orleans in 1940-1941 and Harrisburg in 1943. In 1940 the team played as an independent but returned to the Negro American League the following year. After disbanding for a year, they made a final effort to organize in 1943, when they were entered in the Negro National League, but withdrew early in the spring to barnstorm against a team headlining Dizzy Dean, and were promptly suspended by the league.