In Space Marine, the player is constantly in the middle of the action, there is no time to take cover. The orcs come in large numbers and the player hits, shoots and cuts his way through them. Titus can quickly switch between close-range weapons, such as his saw and hammer, and many types of firearms for the longer ranges.

In addition to the story mode, Warhammer 40,000: Space Marine also has a multiplayer mode where two teams, the Space Marines and the Chaos Space Marines, compete against each other. In this multiplayer game, in which up to 16 people can play at the same time, gamers earn experience points to purchase new weapons and armor.