Axl Rose, frontman of Guns N' Roses, made a deal with Activision to include the song "Welcome to the Jungle" for use in the game with a promise of not including any reference of ex-guitarist of GNR, Slash, in the game. However, Activision still included Slash, and his post-Guns N' Roses band, Velvet Revolver. Axl Rose attempted to sue Activision for $20,000,000 for their breach of contract, but did so too late and thus it was dismissed in court.

Axel's alternate outfit is a tribute to fallen guitarist Dimebag Darrell from the bands Pantera and Damage Plan.

Digital sales of DragonForce's song "Through the Fire and the Flames" rose from 2,000 a week up to almost 38,000 per week over a period of 3 months because of its inclusion in Guitar Hero III.

Before Neversoft started development of Guitar Hero III, Harmonix envisioned the game to take place in a dystopian future where rock music was banned.