Zeno Clash is a first-person fighting game set in the surreal Zenozoik fantasy world. The player controls Ghat, a Corwin of the Free. He is chased away from the city Hastledom, and is hunted by his many brothers and sisters who are all children of Father-Mother, a hermaphrodite creature who is the head of the clan. He escapes with the female character Deadra, who assists him as an AI-controlled character during the course of the game.
The story is told in two storylines, alternately chronological sequences of his journey, as well as through flashbacks leading up to how Ghat killed Father-Mother. Fighting is largely focused on brawling, with Ghat's fists as the primary weapons. He is able to deliver single blows, combine them into combos and charge for large ones. Similar to 2D beat-em-ups, hurt characters can be held and kicked or punched for additional damage, and kicked when they are on the ground. Ghat is also able to block most attacks, and dodge to attack from the sides. Blocking and running around however drains a stamina bar, and it needs some time to fill up again. Many opponents carry around melee and long-distance weapons Ghat can also wield. Health is restored by picking up berries.
Most of the fighting sequences take placed in enclosed areas, with a limited amount of enemies. There are also boss sequences where different tactics need to be used. Certain enemies can only be damaged through large weapons. The game uses a targeting system where it is possible to lock on to a certain character to keep it into view. Next to the main game, there is also a Challenge mode set in a tower with different consecutive arena levels with all the enemies you can encounter.