Lepidus was among Julius Caesar's greatest supporters. He started his cursus honorum as a praetor in 49 BC, was placed in charge of Rome while Caesar defeated Pompey in Greece, and was rewarded with the consulship in 46 BC after the defeat of the Pompeians in the East. When in February 44 BC Caesar was elected dictator for life by the senate, he made Lepidus "Master of the Horse", effectively deputy in the dictatorship.
Their brief alliance in power came to a sudden end when Caesar was assassinated on March 15 44 BC (the Ides of March). One of the ringleaders of the conspiracy, Gaius Cassius Longinus, had argued for the killing of Lepidus and Mark Antony as well, but Marcus Junius Brutus had overruled him, saying the action was an execution and not a political coup.
After Caesar's murder, Lepidus, despite assuring the Senate of his loyalty, allied himself with Mark Antony in a joint bid for power. But Caesar had left an heir: Gaius Julius Caesar Octavianus, his great-nephew and adopted son in Caesar's will. Octavian, Antony and Lepidus met on an island in a river near Mutina (modern Modena), their armies lined along opposite banks, and formed the Second Triumvirate, legalized with the name of Triumvirs for Confirming the Republic with Consular Power (Triumviri Rei Publicae Constituendae Consulari Potestate) by the Lex Titia of 43 BC.
Unlike the First Triumvirate of Caesar, Pompey, and Crassus, this one was formally constituted. In effect, it sidelined the consuls and the senate and signalled the death of the Republic. The triumvirate's legal life span of five years was renewed in 37 BC by the treaty of Tarentum for an equal period of time.
After the pacification of the east and the defeat of the assassins' faction in the Battle of Philippi, during which he remained in Rome, Lepidus assumed rule of the western provinces of Hispaniaand Africa. During the Sicilian revolt Lepidus raised a large army of 14 legions to help subdue Sextus Pompey. For a while he managed to distance himself from the frequent quarrels between his colleagues Antony and Octavian; however, in 36 BC an ill-judged political move gave Octavian the excuse he needed: Lepidus was accused of usurping power in Sicily and of attempted rebellion and was forced into exile in Circeii. He was stripped of all his offices except that of Pontifex Maximus. Spending the rest of his life in obscurity, he died peacefully in late 13 BC or early 12 BC.
Lepidus was the son of Marcus Aemilius Lepidus; his mother may have been a daughter of Lucius Appuleius Saturninus. His brother was Lucius Aemilius Lepidus Paullus. He married Junia Secunda, sister of Marcus Junius Brutus and Junia Tertia, Cassius Longinus's wife. After the Battle of Philippi, Lepidus managed to protect Junia Secunda and her mother Servilia from execution.
Lepidus and Junia Secunda had one child, Marcus Aemilius Lepidus the Younger.
- He has a minor role in the Shakespeare play Julius Caesar, in which he is called "a slight, unmeritable man". He also appears in Antony and Cleopatra, in which he is a passive associate of Octavian, and gets very drunk with Antony and Sextus Pompey.
- The triumvir Marcus Aemilius Lepidus is the principal character of Alfred Duggan's 1958 historical novel Three's Company. As the novel's title implies, it is centered on the second triumvirate, but relates the period through the lens of Lepidus' life and experiences.
- In the BBC/HBO series Rome, Lepidus is portrayed by Ronan Vibert, although much of his involvement in the 2nd Triumvirate is not included in the series' plots. He is portrayed as an inadequate rival for the powerhouses of Octavian and Antony.