Castlevania: Lords of Shadow begins in the year 1047, during "the end of days". A dark spell has stopped the souls of the deceased from leaving, and the world has become a place where evil creatures wreak chaos and death on the living.

In these dark times, Gabriel Belmont, a holy knight from the Brotherhood of Light serves to defend innocent people by destroying these evil creatures. Unfortunately, Gabriel's wife, Marie, is killed by the evil creatures, and her soul is trapped in limbo. As her soul lingers, she realizes what is at stake and guides Gabriel to battle the Lords of Shadow. Gabriel's quest is to defeat the Lords of Shadow and obtain the "God Mask", a relic he believes can bring back his wife. Will Gabriel succeed in his quest and bring salvation to the world?