Defiance is an MMO third-person shooter set in a persistent universe. It was made as a tie-in to the US SyFy television series of the same name. The game takes place several decades into the future in the San Francisco Bay Area, following a war between the human race and an alien race known as the Votans. Due to their planet being destroyed, The Votans arrived on Earth hoping to find a vacant planet where they could set up a new civilization. Humans and Voltans clashed, unleashing alien power that terraformed the earth, causing the Earth's surface to change dramatically. Old species and plants became extinct, while new species emerged. The player plays as an "Ark Hunter" hired by a wealthy industrialist to search for hidden alien power.

Defiance features advanced character customization. Players have the ability to customize everything from the clothes they are wearing to their facial hair style. Players also have the option to be a Human or an Irathient, a humanoid alien species that are similar to humans. There is not a strict class system, and instead allows players to choose from one of four origins, which are veterans, outlaws, machinists, and survivalists. Origins do not affect the abilities, weapons, or outfits the player can choose, and instead just serve as a starting point and background for your character. The game's key feature is its Arkfall Events, which are dynamic events which pit humans, aliens, and monsters against one another in order to obtain expensive alien technology.