The game is set in the fantasy world of Zenozoik, and follows Ghat, a young man who is on the run from his vengeful siblings, and Deadra, his female companion, as they travel through strange and exotic lands.

In the main story mode, players assume the role of Ghat and progress through the world of Zenozoik, visiting various locations in a linear sequence.

While there is a strong focus on unarmed combat, Ghat can also obtain unconventional melee and ranged weapons by several means, such as disarming enemies.

[1] In addition to the single-player story, Challenge Mode allows the player to defeat enemies while climbing a tower or descending into a pit.

[5][6] During their travels away from Halstedom, Ghat explains to Deadra through partially interactive flashbacks the events that led up to his attempt on Father-Mother's life.

When Ghat returns from hunting rabbit-like creatures, he discovers a blind mercenary known only as the Hunter, who points a rifle at Deadra's head while she sleeps.

[13] Their last project, Zenozoik, was far larger in scope than Zeno Clash, and attempted to incorporate the disparate elements of shooting, role-playing, melee combat and sandbox gameplay.

They also likened it to "Dark Messiah meets Double Dragon", and stated that they have drawn a lot of inspiration from traditional fighting games—this includes "versus screens" sliding in before combat is initiated.

[14] Regarding the art style, they cited Hieronymus Bosch's paintings and John Blanche's "punk fantasy" illustrations as visual inspirations.

[15] They stated that publishers were unsure if consumers could relate to the art direction, but nonetheless stuck to their vision, creating a game that looks unlike anything else on the market.

[16] To get their desired organic look, they used static props exported from 3D Studio Max with pre-rendered lighting instead of using brush-based geometry that Source was specialized for.

[26] ACE Team continued to provide support post-release, releasing character models for use with another Source engine game, Garry's Mod,[27] several new Challenge levels as free downloadable content,[28] and a software development kit.

[30][31] ACE Team later claimed that their unique approach, while probably not changing the minds of potential infringers, accidentally generated press which helped to market the product.

[32][33] In January 2009, Zeno Clash was a nominated finalist in the Independent Games Festival yearly competition, in the category of Excellence in Visual Art.

[57] Jason Ocampo of IGN remarked in his review that "thanks to smart design and storytelling, it feels refreshingly original and completely compelling.

1Up.com's Scott Sharkey felt that the first-person fisticuffs were convincing when combined with camera motion; he compared such aspects to Mirror's Edge.

[58] Eduardo Reboucas of GameRevolution felt that the trigger-based controls of the Ultimate Edition took some getting used to and that some encounters with enemies can occasionally become frustrating.

[62] ACE Team expressed a desire to incorporate elements of role-playing games that were present in their previous abandoned project, Zenozoik.