Ancient Greek writers called the island "Melite" which, over the centuries evolved to become the Slavic name, Mljet. Illyrian remains are on the island in the form of graves and fortifications made of roughly cut stone blocks which can be seen on the hills. It was also populated by the Romans until 535 when it fell under control of the Byzantine empire. A succession of rulers followed until 1151 when the island was given to Benedictine monks from the Italian province of Puglia. It was the Benedictines who built a monastery on Sv Marija islet in Veliko Jezero.

Venice and Dubrovnik competed for control of Mljet but Dubrovnik prevailed and Mljet became part of the Dubrovnik republic in the mid-14th century. During the Cyprian war Turkey and Venice plundered Mljet and pirates devastated the island several times during the Cretan war (1645-1649). Nevertheless it remained part of the Dubrovnik republic until 1808 when Dubrovnik fell.

During WWII Mljet harboured an active unit of Partisans which remained during the German occupation of 1944. It was liberated on September 13, 1944.