The game starts at the map screen, where the player can select currently available missions or access in-game features including a shop, casino, and arena. There are always several generic missions available, as well as story quest missions. Additionally, the player can play a bonus mission each day for a small gold bonus.

Cash and gold can be used to purchase weapons, equipment, and character upgrades. Weapons are mostly based on real-life firearms such as the Colt M1911A1 and AK-47. Dead Trigger offers pistols, rifles, shotguns, machine guns, and melee weapons. Items include medkits and sentry turrets. Character upgrades include additional item slots and health.

Dead Trigger offers a basic progression system where the player gains experience points and can level up, but leveling up only unlocks new weapons and items in the shop.

All missions fall into several basic types, such as defending doors or killing a certain number of zombies. There are a limited number of locations that are reused frequently in both story and random missions. Another game mode is the arena, which is a wave-based survival mode.