Mark Antony began military service in the eastern Mediterranean and later joined Julius Caesar's campaigns in Gaul. As tribune in 49 BCE he defended Caesar's interests during the confrontation with the Senate and fled to Caesar's camp as civil war approached. He held important commands, including at Pharsalus in 48, and administered affairs in Italy during Caesar's absence.

Antony was consul with Caesar in 44 BCE. After Caesar's assassination, his funeral speech helped turn popular anger against the conspirators, although its exact wording cannot be recovered from later literary versions. He initially attempted to control the settlement but faced the emergence of Caesar's heir Octavian and opposition from Cicero. Fighting around Mutina in 43 ended without securing his position. He then reached an agreement with Octavian and Lepidus, creating the legally authorized Second Triumvirate. Its proscriptions confiscated property and killed opponents, including Cicero.

At Philippi in 42 BCE, Antony and Octavian defeated Brutus and Cassius. Antony took primary responsibility for the eastern territories, pursuing revenue, alliances, and war against Parthia. His relationship with Cleopatra VII joined personal attachment with the resources and politics of Egypt. Marriage to Octavian's sister Octavia in 40 temporarily supported cooperation, but disputes continued. His Parthian campaign in 36 suffered heavy losses, followed by a more successful intervention in Armenia. The public distribution of eastern titles and territories to Cleopatra's children in 34 gave Octavian material for portraying him as disloyal to Rome.

The alliance collapsed into renewed civil war. Octavian presented the conflict as a war against Cleopatra and exploited Antony's rejection of Octavia and eastern associations. At Actium in 31 BCE, the fleet under Octavian's commander Agrippa defeated the forces of Antony and Cleopatra. They withdrew to Egypt, where their position deteriorated as troops and allies deserted. Antony died by suicide when Octavian captured Alexandria in 30. His career illustrates the power of military allegiance and provincial resources in the Republic's final struggles. Later accounts were shaped by the victor's political interests and by the dramatic appeal of his relationship with Cleopatra. Those traditions should not eclipse his substantial military experience, administrative role, participation in political violence, and unsuccessful bid to dominate the Roman state.