In Space Marines the player engages enemies through a third-person view with both melee and ranged attacks. As a Space Marine, you are given enhanced regenerative abilities and an Iron Halo shield. When health gets low, performing executions can allow Titus to get a portion of his health back. You are accompanied by Sidonus and Leandros for most of the missions, though in some instances you will have to go on solo missions. The game features a fury system that, when filled up, allows the player to either slow time for aiming or perform devastating melee attacks. Space Marine does not feature a cover system.

Your starting weapons include a Combat Knife and a Bolt Pistol, though the player can acquire other weapons ranging from Plasma Guns and Lascannons to mighty Thunder Hammers. The game includes a new weapon not featured in the actual table-top game known as the Vengeance Launcher, which can shoot mines.