Nyt ensimmäistä kertaa Guitar Hero fanit saavat rokata uudella langattomalla kitaralla. Eksklusiiviset Gibsonin kitarat sisältävät nyt vaihdettavat faceplatit, joilla jokainen voi muokata kitaransa itsensä näköiseksi. Uusi näppäinten väritys mahdollistaa entistä paremman tuntuman ja rock kokemuksen.

Lisänä pelaajat pääsevät taistelemaan toistensa kanssa "battle-mode":ssa On-Linessa.

Biisilista:

* Miss Murder - AFI
* Through Fire and Flames - Dragonforce
* Number of the Beast - Iron Maiden
* 3's and 7's - Queens of the Stone Age
* Suck My Kiss - Red Hot Chili Peppers
* Raining Blood - Slayer
* Reptillia - The Strokes
* Paranoid - as made famous by Black Sabbath
* Cities on Flame - as made famous by Blue Oyster Cult
* Mississippi Queen - as made famous by Mountain
* La Grange - as made famous by ZZ Top
* Slash's Original Boss Battle Recording
* Welcome to The Jungle - Guns N' Roses
* Paint It Black - The Rolling Stones
* Cherub Rock - Smashing Pumpkins
* Sabotage - Beastie Boys
* The Metal - Tenacious
* My Name is Jonas - Weezer
* Knights of Cydonia - Muse
* Even Flow - Pearl Jam
* Lay Down - Priestess
* Cult of Personality - by Living Colour
* Rock and Roll All Nite - as made famous by Kiss
* School's Out - as made famous by Alice Cooper
* Rock You Like a Hurricane - as made famous by Scorpions
* Slow Ride - as made famous by Foghat
* Barracuda - as made famous by Heart