According to mythology, Misenum was named after Misenus, a companion of Hector and trumpeter to Aeneas. Misenus is supposed to have drowned near here after a trumpet competition with the sea-god Triton, as recounted in Virgil's Aeneid.
In ancient times, Misenum was the largest base of the Roman navy, since its port (Portus Julius) was the base of the Classis Misenensis, the most important Roman fleet. It was first established as a naval base in 27 BC by Marcus Agrippa, the right-hand man of the emperor Augustus.
Pliny the Elder was the praefect in charge of the naval fleet at Misenum in AD 79, at the time of the eruption of Mount Vesuvius, visible to the south across the Bay of Naples. Seeing the beginnings of the eruption, Pliny left for a closer view and to effect a possible rescue, and was killed by the eruption. The account of his death is given by his nephew Pliny the Younger, who was also resident in Misenum at the time.
Misenum is one of the main settings in Robert Harris' novel Pompeii, whose protagonist, Attilius, works as the aquarius at the Piscina Mirabilis (the terminal reservoir into which the Aqua Augusta aqueduct emptied).
In the novel Ben-Hur Misenum is the location of a villa owned by Quintus Arrius later bequeathed to his adopted son Judah Ben-Hur. The Ben-Hur family would later live in Misenum.