This game offers the only visual explanation of how Dante's sword Rebellion remains on his back without being fastened to his clothes. (His abilities allow him to "summon" the sword at will through the Angel markings on his back.)
Unlike previous DMC installments, Dante and Vergil do not transform into demonic "creatures" when their devil triggers are activated. They remain in human form and their powers are portrayed by a change in their hair color, eye color, skin color, and clothing.
In the story for the original games, Virgil was the older of the twins, where in this game Dante is the senior brother.
Dante primarily wields his sword rebellion with his left hand, unlike previous installments of DMC where he used his right hand.
The three scar-like marks on Mundus' forehead are an inverted representation of his three-eyed demon form. (As seen in previous games) During the fight with Lilith, it can be seen that Mundus' spawn also has three eyes.