[1] New York City FC entered the playoffs as the defending MLS champions, but were eliminated in the conference finals by the Philadelphia Union.

Los Angeles FC entered as Supporters' Shield winners and won their first MLS Cup, defeating the Philadelphia Union in a penalty shoot-out.

The 2022 playoffs marked the first since 2008 where no teams from the Pacific Northwest region (including 2021 finalist Portland Timbers) qualified; Seattle Sounders FC failed to qualify for the first time in their MLS history, snapping a league-record thirteen-year playoff streak.

The higher-seeded teams in each conference as determined by regular season ranking hosted the matches.

The highest-ranked team remaining in the overall table (Los Angeles FC) hosted the match.