Green Day: Rock Band is the second major release in the Rock Band series designed around a specific band, in this case the American punk rock group from California.

Gameplay remains the same as in other games of the series: players use their instrument controllers to play guitar, bass and drum parts and sing vocal parts, matching notes on the screen in rhythm with the music. Vocal harmonies, earlier seen in The Beatles: Rock Band are also featured, allowing three players to sing certain parts together. The game offers Quick Play and Career modes. In Quick Play, all included songs can be played from the start, while Career mode moves through several setlists, unlocking more songs along the way. Completing challenges in Career mode unlocks pictures and videos of the band. The game features three different venues and puts the band members into various outfits, all depending on the song being played. A Score Duel mode features multiplayer duels against players playing the same instrument part on the same song.

The game features 44 tracks (equaling 47 songs since some are arranged in medleys), including the entirety of the band's best-selling albums Dookie, American Idiot and 21st Century Breakdown (minus six tracks released as DLC for earlier Rock Band games), and selected tracks from Insomniac, Nimrod and Wanted. On the PS3 and Xbox 360 versions, the tracks can be exported for use in other Rock Band games for a fee. The 21st Century Breakdown DLC tracks are also supported for play.