Warhammer 40.000: Space Marine is a third-person shooter set in the Warhammer 40.000 universe. The player takes the role of Captain Titus, member of the Ultra Marines, an elite section of the Space Marines. His mission: driving back the Orc invasion on the industry planet Graia. A super weapon is stored there and the Orcs must not grab it. He also has to deal with the Chaos Marines and other alien races.

Gameplay is simple: walking - mostly together with two fellow Marines - through the levels and kill the enemy hordes. Titus has a multitude of ranged and melee weapons to his disposal, but the focus lies on melee combat. Like most similar games, there are combo attacks which are performed by using the correct buttons with the right timing. Additionally he can unleash especially powerful attacks when he earned enough fury by killing enemies. Titus also has to solve rail shooter sequences and sometimes he gets a jet pack along with a more open level design. To account for the Space Marine class character, there is no cover system and a mix between regenerative shield and health which can be regained by performing executions.