It had been verified that the game would launch for PS4, Xbox One, and PC. EA verified that Madden NFL would be coming later to Stadia, making it the first Madden game to start Google's cloud streaming platform. It was also announced that Mut 21 coins will be accessible on PS5 and Xbox collection X later in year.

EA confirmed that the sport would allow free updates to versions for those who own it on Xbox One or PS4. However, EA put restrictions set up, for purchasing the game, using a limited time window and then for redeeming the update. Following criticism for the decision, EA extended the window, stating that players can update to variations at any time prior to the launching of Madden NFL 22.

In May, it was announced that Madden NFL 21 would be formally unveiled using a reveal trailer on June 1. However, shortly EA pushed the game's reveal due to the nationwide protests after the killing of George Floyd. The game was later revealed in complete later in June. Because of Washington Redskins announcing it would be changing its name to drop the team's controversial moniker, EA announced the team's latest logo and title would be removed out of Madden NFL 21 too, and could be replaced with a generic team name and emblem until new ones had been finalized, which would then be inserted into the game later.

EA confirmed that Madden NFL 21 would not feature cross platform multiplayer gameplay.

Madden NFL 21 introduces several new gameplay mechanics to the series. Rather than just one skill button, skills are performed through the ideal analog tick. Skills could be carried out in combos and strung together, including slides, jukes, spins, and barriers. The ability rod is used for defending as well, together with pass rush moves and block-sheds now being on the right analog stick.

Defending sees changes in some other regions. Tackling animations are now triggered based on places, which means their own body positions are adjusted by defenders and handle based on they are on the field, and have been revamped. Whilst dive tackling has been improved also, breakdown handling has also been added. AI has also been improved, with buy Mut 21 coins plays being made smarter by opposition quarterbacks and reacting to players' actions more suitably.