There are 64 songs total in the PlayStation 2 version while there are 74 songs total for the later Xbox 360 version. The Xbox 360 version adds an additional 24 downloadable songs via Xbox Live Marketplace (bringing the total to 98 songs).

There are 40 songs in the main Career mode for the PlayStation 2 version, and 48 songs in the Xbox 360 version. Songs are organized by tiers that are related to the song's difficulty and there are differences between the PlayStation 2 and Xbox 360 ordering due to the extra songs. Each tier at a given difficulty is unlocked in order, and a tier is completed once three to five songs (depending on the difficulty level) and the tier's encore song are successfully completed. Once a song is unlocked in a tier at any difficulty, it is available for the quick play, competitive, and co-operative modes.

Most songs in the game are covers of the original songs performed by WaveGroup Sound, but there are some master recordings as indicated below. Each song has a lead guitar track and either a bass or rhythm guitar track that can be played in practice or cooperative modes.

There are 24 bonus songs in the PlayStation 2 version of Guitar Hero II and 2 additional songs for the Xbox 360 version. All bonus songs are unlockable by using in-game money to buy them within the game's store. Once purchased, they are playable in quick play, competitive, and co-operative modes. The song "Raw Dog" by The Last Vegas was selected as part of the "Be a Guitar Hero" content for the release of Guitar Hero II. All bonus songs are master recordings, and where marked, include rhythm guitar rather than bass guitar tracks.

The Xbox 360 version of the game allows for the use of downloadable content available through Xbox Live Marketplace. These are typically released as packs of three, or as single song. These packs include songs from the original Guitar Hero for the PlayStation 2. Additional packs consist of songs that have not been featured in Guitar Hero before, and are masters, even though some are indicated as covers in the game.