Major League Indoor Soccer (MLIS) is an indoor soccer league that began play in 2022 and based in the United States.

Major League Indoor Soccer was announced in August 2022 to begin play in December of the same year. The league launched with 12 teams divided among three divisions: East, Central, and South. The league's first game featured Rapid City FC defeat the Cincinnati Swerve 8-1 at GameTime Training Center in Fairfield, Ohio.

On March 29, 2024, the league announced a merger with the National Indoor Soccer League, keeping the Major League Indoor Soccer name.

Bernie Lilavois would be named new commissioner of the MLIS in November 2024.

In July 2025, MLIS announced the launch of Major League Indoor Soccer Extended (MLISX), an amateur league designed to provide a pathway to professionalism for players, coaches, and officials. The league will be operated by MLIS, but each franchise will be independently owned and managed.

On August 18, 2022, Chicago (Mustangs), Cleveland Crunch, and Grand Rapids (Rapid City FC) were announced as charter teams.

Former NISL team Central Florida Crusaders relocated to Toronto and joined the MLIS ahead of the 2024-25 season as the Canadian Crusaders, the league's first team based outside the United States.

Panathinaikos Chicago would join the MLIS for the 2024-25 season, though they would not return for 2025-26.