Red Faction Guerrilla takes place on Mars, shortly after the events of the previous game in the Red Faction series. You play as Alec Mason, a newly recruited miner who has just come to Mars looking for work. This time you find yourself fighting against the Earth Defense Force (EDF), which was your ally in the last game, and being accused of committing terrorism on behalf of Red Faction. Once this happens, Alec has no choice but to join Red Faction and try to free six EDF-controlled zones on Mars.

Liberating zones from the clutches of the EDF is pretty easy—you simply need to reduce their control rating in each area. You do this by completing missions for the Red Faction and by destroying specific EDF-controlled buildings in the zone. Every time a mission is completed or an EDF-controlled building is destroyed, the morale of the people in that sector increases. The higher their morale, the more inclined they will be to help you when you are exchanging fire with the EDF.

There are several side missions as well as story missions in each zone. Side missions usually involve freeing hostages or blowing up specified buildings, and are generally a lot more monotonous than the story missions. There are also a few challenges that you can complete in each zone, which award you money if you finish the challenge within the specified time. Pressing select brings up a map of your current zone and displays any available missions. Once you've chosen a mission, a set of arrows will appear on the ground that guide you towards the starting point. This is extremely useful, as the Martian terrain determines which way you need to go to reach a mission. Each zone is quite small, and the game world is nowhere near the size of other open world games, so getting lost here is not an issue at all.

In addition to being the focus of many missions in RFG, destroying structures also allows you to collect salvage. Salvage is essentially the currency of Red Faction Guerrilla, and can be used to buy and upgrade weapons, armor, and tools. There are a wide variety of weapons available; you start the game off with your basic sledgehammer, but you'll eventually be able to get a rocket launcher, jet-pack, and a whole lot more. RFG also includes a number of vehicles you can drive, which differ in speed and strength. Choosing the right vehicle will make a difference in some missions; for example, stronger trucks will be needed for missions where you are ramming into things and being chased by the EDF.

If you've played any Red Faction game before, you'll know that destructible environments are key to the series's gameplay. It's fortunate then, that the structures in Red Faction Guerrilla are highly destructible—a testament to Volition's excellent physics engine. For this reason, the main goal of Red Faction Guerrilla is to destroy things—a task which can be done in a variety of ways. The sledgehammer allows you to take out walls and buildings, but a quicker method is to surround a structure with mines and detonate them from afar. Unfortunately, the novelty of this destruction does diminish after an hour or so, and if that happens to you, you're unlikely to be happy with the rest of what the game has to offer.