[7] It is the first MLS All-Star Game to be played in the Los Angeles area since 2003, which was hosted by the LA Galaxy at the Home Depot Center, now known as Dignity Health Sports Park.

[9] The league announced on June 9, 2021, that the All-Star Game against Liga MX would be played on August 25 at Banc of California Stadium.

New England players Carles Gil and Tajon Buchanan withdrew as well as Minnesota United midfielder Emanuel Reynoso.

[11] Six members of the starting XI were selected from Seattle Sounders FC, tying the record set by D.C. United in 2006.

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

Nahuel Guzmán and Jorge Sánchez were called up as replacements for José de Jesús Corona and Fernando Navarro who withdrew due to injury.

The MLS All-Star Skills Challenge was played on August 24 at Banc of California Park between eight players from each team in five events.