In the game's primary single-player mode, titled GH Live within the game, the player completes songs while experiencing full-motion video taken from the first-person perspective of a band's lead guitarist.

The layout was also designed to provide a new challenge to experienced players, including more realistic simulations of chords. Griffin was more favorable of the on-disc set list, finding that the tracks represented "the music landscape as it is rather than as it was". Miller stated that the microtransaction "structure is exploitative", preventing him from easily accessing his favorite songs to play and making him frustrated with the game in the long run. The GHTV mode also received mixed reception for its reliance on microtransactions, and the inability to permanently purchase songs to own.GHTV offered curated music video shows with host segments wrapped around playable songs; the first such show features songs selected by the band Avenged Sevenfold and included commentary by the band on these selections. It's actually real people in the crowd, backstage and playing in the band with you which makes it feel like your important and motivated to play well. The game was released for PlayStation 3, PlayStation 4, Wii U, Xbox 360, and Xbox One in October 2015. To calculate the overall star rating and percentage breakdown by star, we don’t use a simple average.

Tan noted that in addition to either the time to complete the challenges or in-game currency to unlock the show, the player would have to complete the show in one of the ranked positions to earn the offered prize, and if they failed, they would have to repeat that process again. The core gameplay of Guitar Hero Live was rebuilt from scratch; developer Jamie Jackson explained that the goal of the game was to bring "big innovation" to the franchise rather than continue with the same format used by previous games. Members of these fictional bands were selected through auditions prior to filming, making sure that they could recreate the actual performance of a song, as well as mixing and matching members of ensemble groups to get the right look and feel.I did feel although there is a lot I liked about this part of the game, it felt too simple, was over too quickly as there is only two main venues, and it felt like it wasn't the main part of the game. The iOS app was also delisted as its functionality would also cease with the shut down of the GHTV servers. The great thing about this is the actual music videos of the songs play in the background, which is really cool.

In an update in December 2015, players on GHTV had an opportunity to be randomly pitted in a head-to-head challenge against another player of similar skill level, about twice every half-hour. Hero Power, replacing Star Power from previous Guitar Hero games, is collected by correctly playing marked series of notes on the track; Hero Power can be accumulated, marked as on-screen guitar picks next to the track, to be used at later times. Jackson explained that the feature and its curated playlists were "about discovering music as much as it is about going and finding music you know you already like". Songs in GH Live mode (below) also includes vocals, allowing players to sing along in tone with the song's lyrics using a connected microphone. As with previous games in the series, the goal is to use a special guitar controller to match fret patterns displayed on a scrolling note pattern on screen in time with the music.

Prior to filming with the Bolt, an actor outfitted with motion and position detectors acted out the song with the other band actors; these movements were recorded and then used to direct the Bolt as it replaced the actor in subsequent takes. Two hundred songs were playable on GHTV at launch, and the developers plan on adding new songs to GHTV on a regular basis.