The league had 28 clubs following the addition of Charlotte FC as an expansion team.

The regular season began on February 26 and concluded on October 9.

[1] New York City FC entered the season as defending champions, having defeated the Portland Timbers in MLS Cup 2021, while the New England Revolution entered the season as the reigning Supporters' Shield winners.

Western Conference regular season and playoff champions, Los Angeles FC won their second Supporters' Shield and their first MLS Cup, defeating the Eastern Conference regular season and playoff champions, the Philadelphia Union, in a penalty shoot-out.

A total of 476 matches were played over the course of the regular season and drew an average attendance of 21,033.