In Red Faction: Guerrilla, the player takes the role of a guerrilla member, Alec Mason, as he assists the Red Faction to disrupt and overthrow the power of the Earth Defense Force (EDF) on Mars. This is presented to the player in a third person perspective, a departure from the series' previous two games which were first person shooters, a change that Volition claims to help the player see and appreciate the surroundings as they are destroyed. Much of the game centers around the game's Geomod 2.0 engine, which allows for buildings and other structures to take damage, fall apart and collapse. In many cases, destroying buildings will leave behind salvage, the game's form of currency, which can be used along with salvage rewarded by completing missions to unlock new weapons and upgrade existing ones when visiting one of the Red Faction safehouses. During campaign mode, the player is always equipped with a sledgehammer-like weapon, used mainly for destroying buildings and crushing enemies, along with up to 3 other weapons or explosive devices. The player also has the opportunity to control armed vehicles such as tanks and walkers for more destructive options.
The game plays out in an open world representing a terraformed area of Mars' surface. The world is broken into six distinct areas: Parker, Dust, Free fire zone, Oasis, the Badlands, and Eos. The player must successfully free each area from EDF control before moving onto the next; should the player wander into as-yet-unlocked areas, they will be shot at will by the EDF forces. The player can traverse these on foot or by hijacking one of the numerous vehicles that travel its surface; the player is provided with both a surface and mini-map and a GPS indicator to direct them to a target location. In order to liberate an area of EDF control, the player must complete a number of specific 'story missions', as well as completing other actions, typically the destruction of key EDF targets, that reduce the EDF's presence in the area. At the same time, the player can complete various side missions, which range from rescuing hostages, retrieving new vehicles, to preventing raids on Red Faction bases, and the like, to increase the morale of civilians in the area. Players may also be rewarded with salvage for completing these tasks. Other actions, such as letting civilians die, will lower morale, while actively killing civilians will lower morale faster. Should the player engage EDF forces in an area with high morale, there is a good chance that civilians will join the Red Faction and fight alongside the player. Once the player has worn down the EDF presence in a sector to zero, a final mission will be available allowing the player to completely secure the sector for the Red Faction. Once this has been completed for a sector, it will be freely traversable, with no danger of conflict with EDF forces. However, as the EDF forces are diminished, particularly in the later sectors, the player may become the target of the Marauders, a diverse nomadic group that survive by ransacking both Red Faction and EDF structures alike.