RedOctane, then a company primarily in the manufacture of unique game controllers, was inspired in 2005 to create Guitar Hero based on their experience with creating hardware for Konami's GuitarFreaks arcade game, and enlisted the help of Harmonix Music Systems, who had previously developed several music video games, for development duties. The first game in the series was made on a budget of $1 million. The series became extremely successful, leading to, in 2007, the acquisition of RedOctane by Activision, while Harmonix was acquired by MTV Games and went on to create the Rock Band series of music games in the same vein as Guitar Hero. Activision brought Neversoft (primarily known for their Tony Hawk series of skateboarding games) on board for future development duties. Additional companies, such as Vicarious Visions, Budcat Creations, Machineworks Northwest, and Aspyr Media have assisted in the adoption of the games for other systems.

The game currently has seven major releases and four expansions on gaming consoles, and with spinoffs for Windows and Macintosh systems, mobile phones, the Nintendo DS, and an arcade game, with several more titles announced for future release. The Guitar Hero franchise has become a cultural phenomenon and learning and development tool for medical purposes, and has impacted both the video game and the modern music industry. The first game in the series was considered by several journalists to be one of the most influential video games of the first decade of the 21st century. The series has sold more than 25 million units worldwide, earning US$2 billion at retail, claimed by Activision to be the 3rd largest game franchise after the Mario and Madden NFL franchises; the third main title of the series, Guitar Hero III: Legends of Rock is also claimed by Activision to be the first single video game title to exceed $1 billion in sales.

Guitar Hero was created from a partnership between RedOctane, then their own company that produced specialized gaming controllers, and Harmonix Music Systems, a music video game development company who had previously produced Frequency, Amplitude and Karaoke Revolution. RedOctane was seeking to bring in a GuitarFreaks-like game, highly popular at the time in Japan, into the Western markets, and approached Harmonix about helping them to develop a music game around a guitar controller. Both companies agreed to it, and went on to produce Guitar Hero in 2005. The title was highly successful, leading to the development of its successful sequel Guitar Hero II in 2006.

Both RedOctane and Harmonix were experiencing changes in 2006. RedOctane was bought by Activision in June—who spent $100 million to acquire the Guitar Hero franchise—while it was announced in October that Harmonix would be purchased by MTV Networks. As a result of the two purchases, Harmonix would no longer develop future games in the Guitar Hero series. Instead, developing would go to Neversoft, a subsidiary of Activision known for developing the Tony Hawk's series of skateboarding games. Neversoft was chosen to helm the Guitar Hero series after Neversoft founder, Joel Jewett, admitted to the RedOctane founders, Kai and Charles Huang, that his development team for Tony Hawk's Project 8 went to work on weekends just to play Guitar Hero. Activision CEO Bobby Kotick believed that Neversoft would help them bring great games to the series, but on reflection, regretted their decision to not explore Harmonix further as a continued developer for the series. In addition, Activision began seeking other markets for the game; a Nintendo DS version of the series was developed by Vicarious Visions, while a Guitar Hero Mobile series was created for mobile phones. The company also began considering the expansion of the series to band-specific titles with Guitar Hero: Aerosmith. Later, in November 2008, Activision acquired Budcat Creations, another development studio that had helped with the PlayStation 2 versions of Guitar Hero III and World Tour, announcing that they will be helping to develop another game in the Guitar Hero series.

In 2007, Harmonix and MTV Games released a new music title through rival publisher Electronic Arts, called Rock Band. It expanded upon the gameplay popularized by the Guitar Hero series by adding drum and microphone instruments, allowing players to simulate playing songs as bands. Activision followed suit with the release of Guitar Hero World Tour in 2008 which supported multiple instruments. In 2009, Activision expected to triple its Guitar Hero offerings, and in addition to further continuation of the existing main series and expansions, introduced the titles Band Hero, geared towards more family-friendly pop music, and DJ Hero, a game based on turntablism and featuring a number of mixes. With the release of Guitar Hero 5, Activision has considered the series to move away from its heavy metal basis into a more rounded selection of music. Guitar Hero 5 is the first game in the series to use a new version of the series' logo. Previous logos for games used a font with sharper "points" on the letters, which was considered "idiosyncratic with a vengeance" to match the emphasis on heavy metal music that the previous games had. Activision used the services of the Pentagram design studio to refashion the game's logo. Pentagram developed a new font, removing some of the "aggressive odd" features to make the typeface more suitable and amendable to design feature incorporation to other games such as Band Hero and DJ Hero.

The original Guitar Hero was released on the PlayStation 2 in November 2005. Guitar Hero is notable because it comes packaged with a controller peripheral modeled after a black Gibson SG guitar. Rather than a typical gamepad, this guitar controller is the primary input for the game. Playing the game with the guitar controller simulates playing an actual guitar, except it uses five colored "fret buttons" and a "strum bar" instead of frets and strings. The development of Guitar Hero was inspired by Konami's GuitarFreaks arcade game, which at the time, had not seen much exposure in the North American market; RedOctane, already selling guitar-shaped controllers for imported copies of GuitarFreaks, approached Harmonix about creating a game to use an entirely new Guitar controller. The concept was to have the gameplay of Amplitude with the visuals of Karaoke Revolution, both of which had been developed by Harmonix. The game was met with critical acclaim and received numerous awards for its innovative guitar peripheral and its soundtrack, which comprised 47 playable rock songs (most of which were cover versions of popular songs from artists and bands from the 1960s through modern rock). Guitar Hero has sold nearly 1.5 million copies to date.

The popularity of the series increased dramatically with the release of Guitar Hero II for the PlayStation 2 in 2006. Featuring improved multiplayer gameplay, an improved note-recognizing system, and 64 songs, it became the fifth best-selling video game of 2006. The PlayStation 2 version of the game was offered both separately and in a bundle with a cherry red Gibson SG guitar controller. Guitar Hero II was later released for the Xbox 360 in April 2007 with an exclusive Gibson X-Plorer guitar controller and an additional 10 songs, among other features. About 3 million units of Guitar Hero II have sold on the PlayStation 2 and Xbox 360.

Guitar Hero III: Legends of Rock was released in late 2007 for the PlayStation 2, PlayStation 3, Xbox 360, Wii, Win, and Mac platforms. The title is the first installment of the series to include wireless guitars bundled with the game and also the first to release a special bundle with two guitars. The game includes Slash and Tom Morello as playable characters in addition to the existing fictional avatars; both guitarists performed motion capture to be used for their characters' animation in the game.

Guitar Hero World Tour, previously named Guitar Hero IV, is the fourth full game in the series and was released on October 26, 2008 for PlayStation 2, PlayStation 3, Xbox 360, and Wii. Analysts had expected that future Guitar Hero games in 2008 would include additional instrument peripherals to compete against Rock Band; Guitar Hero World Tour was confirmed as in development following the announcement of the merger between Activision and Vivendi Games in December 2007. Activision's CEO Bobby Kotick announced on April 21, 2008 that Guitar Hero World Tour will branch out into other instruments including vocals. Guitar Hero World Tour includes drums and vocals, and can be bought packaged with a new drum set controller, a microphone, and the standard guitar controller. A larger number of real-world musicians appear as playable characters, including Jimi Hendrix, Billy Corgan, Hayley Williams, Zakk Wylde, Ted Nugent, Travis Barker, Sting, and Ozzy Osbourne. Guitar Hero World Tour also features custom song creation that can be shared with others.

Guitar Hero 5, the fifth main entry in the series, was confirmed in December 2008. It was released on September 1, 2009, and includes 85 songs from 83 different artists. The game includes new game modes and features, including its 'Party Mode' which gives players the ability to drop-in and out and change difficulties in the middle of a song. Artists including Johnny Cash, Matt Bellamy, Carlos Santana, Kurt Cobain and Shirley Manson appear as playable characters in the game.