Campaigns are a single-player game mode in which players take part in story-driven battles representing key moments in the Horus Heresy lore. This game mode does not use the player's collection and is perfect for new players or players that wish to broaden their collection.

When a player starts a campaign run, they will play with a predefined deck that is upgraded after every battle. If the player wins a campaign battle, they will be able to choose one of three different packs of three cards to add to their campaign deck. These cards are only used during the campaign run, and are not added to the player's collection.

If the player successfully finishes all the stages of a campaign run, they will receive a crate containing faction cards and a Warlord from that same faction. They will also unlock the possibility to play the campaign from another Warlord's perspective. If the player successfully completes the campaign with all the available Warlords, they will unlock a special final boss that will reward them with an exclusive legendary card back if they manage to defeat it.