He joined the Pompeian party, and organized bands of mercenaries and gladiators to support the cause by public violence in opposition to P. Clodius Pulcher, who gave similar support to the democratic cause. Milo was tribune of the plebs in 57 BC. He took a prominent part in bringing about the recall of Cicero from exile, in spite of the opposition of Clodius.
Milo became praetor in 54, and in that year married Fausta, daughter of the dictator Sulla and ex-wife of Caius Memmius.
In 53, when Milo was candidate for the consulship and Clodius for the praetorship, the two leaders met by accident on the Appian Way at Bovillae and Clodius was murdered (January 18, 52). Milo was impeached; his guilt was clear, and his enemies took every means of intimidating his supporters and his judges. Cicero was afraid to speak, and the extant Pro Milone is an expanded form of the unspoken defence. Milo went into exile at Massilia (today Marseille), and his property was sold by auction. He joined M. Caelius Rufus in 48 in his rising against Caesar, but was captured and executed at Cosa, near Thurii in Lucania.