Dead to Rights is a 3rd-person shooter in which the player is Jack Slate, a police officer in Grant City. On a routine call, he finds the dead body of his father. While trying to find the murderer, he is framed for another murder. Jack becomes a fugitive; his run from the law will take him to various places, from strip joints and hotels to office complexes, and even prison, as an inmate.

When controlling Jack, players can perform various moves, such as grabbing an enemy from behind and using him as a human shield, or tossing a fire extinguisher and shooting it, causing a huge explosion. If Jack does not have a gun drawn, he can disarm an enemy which causes him to steal the enemy's gun, then performing some sort of finish, such as a neck breaker. Initially, only a few disarm moves are available, but more can be unlocked as the game progresses.

Players will sometimes have to control Jack's best friend and partner, his K-9 dog Shadow, which allows enemies to be killed from a distance. In addition, Shadow will fetch their guns and bring them to Jack.

The game also features "adrenaline combat", similar to "Bullet Time" from Max Payne. Jack will then perform slow-motion dives and spins, giving him an advantage, as long as his adrenaline meter holds out.

This is the second version of Dead to Rights (Based on the PS2, GameCube and PC ports) with a rebalanced difficulté (With the addition of difficulty select when starting a new game) and shortned game length (Most puzzle sections are removed and the Prison level was made much more straight forward).