It will be also the club's third season in Major League Soccer (MLS).

In addition to playing in the MLS regular season, St. Louis City SC will compete in the U.S. Open Cup.

Note: Flags indicate national team as defined under FIFA eligibility rules; some limited exceptions apply.

Players may hold more than one non-FIFA nationality.

St. Louis City SC did not qualify for the 2025 Leagues Cup as they were not one of the top 9 teams in the Western Conference for the 2024 season.