Year 546 (DXLVI) was a common year starting on Monday of the Julian calendar. The denomination 546 for this year has been used since the early medieval period, when the Anno Domini calendar era became the prevalent method in Europe for naming years.

• December 17 – Sack of Rome: After almost a year's siege, the capture of a grain fleet sent by the exiled Pope Vigilius near the mouth of the Tiber, and failure of troops of the Byzantine Empire under Belisarius to relieve the city, the Ostrogoths under King Totila plunder Rome and destroy its fortifications.^[1] He then withdraws to Apulia (Southern Italy).
• Winter – Pope Vigilius arrives in Constantinople, to meet with Emperor Justinian I. The future Pope Pelagius is sent by Totila to negotiate with Justinian.

• Audoin murders and succeeds Walthari as king of the Lombards.
• Audoin receives subsidies from Justinian I, to encourage him to battle the Gepids in the Carpathian Mountains.
• Audoin leads the Lombards across the Danube into Pannonia, and becomes an ally of the Byzantines.

• May 5 – After a victory by Calakmul during the First Tikal-Calakmul War, Aj Wosal Chan K'inich is installed as the new ruler of the Mayan city state of Naranjo in Guatemala and reigns until his death in 615.

• The Basilica of San Vitale (Ravenna) is completed by bishop Maximianus, during the Byzantine Exarchate of Ravenna.
• Approximate date – The Diocese of Bangor is established in the Welsh kingdom of Gwynedd, with Deiniol consecrated as first bishop.

• Walthari, king of the Lombards