Space Marines Exterminatus mode pits an elite squad of four Space Marines against hordes of alien enemies in a score based fight to the death. Players can choose the Tactical Marine, Devastator or Assault Marine as well as utilizing any weapons and perks available to those classes.

Each of Exterminatus Mode's scenarios, 'Assault on Hab Center Andreas' and 'Escape From Kalkys Facility,' feature global leader boards challenging players to better their scores by completing dynamic challenges as well as utilizing score modifiers which increase game difficulty in exchange for additional points.

Experience earned while playing this mode counts towards the game's multiplayer ranks, allowing players to earn progression in both Co-Op and multiplayer.