The political and romantic alliance between Mark Antony and Cleopatra VII of Egypt faces imminent destruction as the Roman Empire fractures under the weight of competing ambitions. Antony, a triumvir of Rome, finds himself torn between his duty to the state and his devotion to the Egyptian queen. His neglect of Roman affairs invites the wrath of Octavius Caesar, leading to a series of military and personal confrontations that span the Mediterranean. The narrative unfolds through dramatic dialogue and soliloquies, emphasizing the tension between public duty and private desire. The play operates within the constraints of Elizabethan theatrical conventions, utilizing shifting locales to mirror the instability of the protagonists' world.

Discussion often centers on the complex characterization of the two leads, who are frequently analyzed for their conflicting motivations and grandiosity. Readers frequently highlight the play's linguistic density and the experimental nature of its structure, which deviates from traditional tragic forms. Critics often examine the tension between the Roman values of order and the Egyptian values of excess. The work remains a subject of debate regarding its success as a tragedy, with many focusing on the balance between political commentary and intimate character study. The play's theatricality continues to generate interest among scholars and performers alike.