Published by Ubisoft, the music title will teach users how to play the electric guitar, according to The Hollywood Reporter.
It will come with 45 tracks from artists including The Rolling Stones, David Bowie, Nirvana and The Animals.
As well as offer a standard input jack that is compatible with most electric guitars, Ubisoft is in talks with Gibson to present a guitar bundle at launch for around $200 (£125).
"Guitar Hero is a party game. Rocksmith is a music experience," said senior VP of marketing Tony Key.
"The dream of playing guitar compared to how many follow through - there's a big gap. We will create a new generation of guitar players."
Key said that Rocksmith is one of the publisher's many "games with benefits" that teach players real-life skills, such as exercise techniques in Your Shape: Fitness Evolved and dance moves in Just Dance.
It was also suggested that the title won't suffer the same fate as Guitar Hero because users will never tire of learning how to play the guitar.
Rocksmith will be available in September.