Anarchy Reigns is a third-person brawler fighting game where players choose one of the sixteen available fighters to duke it out in large arenas. Each character is defined through different types of weak and strong attacks with a trademark weapon, a specific fighting style, throws, and different moves that can be chained into combos. They also have access to a move that clears the surrounding area, and many moves are very violent and over the top. It is possible to lock on to a single character and performing evasive actions. A rampage mode is charged up while fighting and there are also bonus items such as shields or rocket launchers. The game incorporates Action Trigger Events (A.T.E.) where actions in the environments can be triggered to influence the combat. Examples of these are plane crashes, black holes or a blitz bombing. The game's backstory describes Earth as a mutant-infested wasteland with monsters and cyborgs following a new world war.

The focus is largely on multiplayer with game modes that include Battle Royale, Capture the Flag, Death Ball, Death Match, Survival and Tag Team, for up to sixteen players simultaneously. There is also a single-player campaign that largely shares the assets of the multiplayer environments. It is split up into two parts, one for Jack Cayman, the Gator Tooth double chainsaw-wielding protagonist from MadWorld and one for Leonhardt "Leo" Victorion,—a new character—an agent of the Bureau's Strike One unit who wields positron blades that can be charged. In the single-player portion, there are many hub areas where a certain amount of enemies needs to be defeated in order to progress and enter new missions. At certain points the campaigns cross over. Jack and Leo are enemies and they both want to hunt down Maximillian Caxton responsible for killing Jack's daughter. After the four stages of each campaign (White and Black), Red is opened up as an additional one.

There are four other characters who return from MadWorld: Big Bull (cyborg with a human brain), Blacker Baron, Mathilda (uses her Iron Maiden spiked club), and Rin Rin (uses the Yanlong blades). Next to Leo the new characters are Ai Rin (with the Huanglong lightning nunchucks), Douglas Williamsburg (with twin pilebunkers), Durga (cyborg bounty hunter who uses martial arts and a revolver cannon attached to his leg), Edgar Oinkie (can turn into a reptile), Fei Rin (with the ice trident Zilong), Garuda (as a mech who can transform into a jet plane), Maximillian Caxton (with both positron blades and tesla blitz), Nikolai Dmitri Bulygin (with tesla coils), Sasha Ivanoff (with an ice blade), and Zero (cybernetic ninja with katanas).