The first name in music instrument gaming returns with a Rock Band-esque focus on full band simulation, the ability for players to create their own music, and more than 80 new tracks in Guitar Hero: World Tour. For the first time in the series, wannabe rock stars can simulate singing and drumming in addition to the familiar strumming of guitar-shaped controllers, and with the addition of a bass guitar, up to four players can form a band and jam together. As with all titles in the Guitar Hero series, gamers must "play" their instruments by rhythmically matching onscreen prompts in order to earn high scores and unlock new songs. The singing mechanic resembles Karaoke Revolution and SingStar in that it requires vocalists to match the pitch and notes of each song, whereas drummers must be timely when depressing the kick drum and striking the proper combination of drum and cymbal pads.

A revamped single-player Career mode lets gamers advance their musician through a series of gigs by playing a specific number of songs, with the option to change difficulty level or instrument at any time. The Band Career mode works in a similar fashion, offering up to four players the opportunity to advance through a full career. Boss Battles also return in a form more akin to previous Face-Off modes, and they no longer feature the attack power-ups used in Guitar Hero III: Legends of Rock and Guitar Hero: Aerosmith. Gamers can use the new "Create-a-Rocker" feature to customize the posture, age, hair, makeup, and tattoos of their unique characters, and real-life rock legends such as Ozzy Osbourne, Jim Hendrix, and Ted Nugent are also playable.

The song list spans several decades and is made up of a diverse selection of master recordings by artists such as: 311, the Allman Brothers Band, the Beastie Boys, Billy Idol, Blondie, Coldplay, the Cult, the Doors, the Eagles, the Foo Fighters, Jane's Addiction, Jimi Hendrix, Korn, Linkin Park, Los Lobos, Metallica, Michael Jackson, Modest Mouse, Motorhead, Nirvana, No Doubt, NOFX, Oasis, Ozzy Osbourne, Pat Benetar, R.E.M, the Sex Pistols, Steely Dan, Sting, the Stone Roses, Sublime, Tool, Van Halen, and Willie Nelson. In addition, players can create their own songs in the Advanced Studio mode by playing tracks for each instrument in either real or slowed time. Songs can be either 1,200 notes long or three minutes in length, but vocal recording is unavailable due to storage issues.