"Julian and Maddalo" is prefaced by a prose description of the main characters. Maddalo is described as a rich Venetian nobleman whose "passions and…powers are incomparably greater than those of other men; and, instead of the latter having been employed in curbing the former, they have mutually lent each other strength"; while Julian is said to be an Englishman of good family, passionately attached to those philosophical notions which assert the power of man over his own mind. He is a complete infidel, and a scoffer at all things reputed holy.

The poem proper then begins with a depiction of the two title characters riding through a Venetian scene and discussing the subjects of religious faith, free will and progress.