António Manoel de Vilhena (1663 - 10 December 1736) was the 66th Grand Master of the Order of Saint John and ruled the island of Malta from 19 June 1722 to his death in 1736).

Manoel de Vilhena was a Portuguese aristocrat of royal descent, son of Sancho Manoel de Vilhena, 1st Count of Vila Flor. Although most Grand Masters of the Order of Saint John were known to keep aloof from the Maltese populace, Grand Master de Vilhena was loved by the Maltese as he strived to better their lot and also set up a number of charitable institutions. To meet the demand for housing and accommodation in Valletta he laid the plans for the building of a suburb in the neighbourhood, Floriana, where his statue still stands today at a prominent place outside the Maglio Gardens. He built Fort Manoel in Marsamxett Creek. In 1731, he built the Manoel Theatre which is believed to be the second oldest theatre in Europe and is still in use today. Grand Master de Vilhena's residence, situated opposite the former Archbishop's Curia in Valletta, has been preserved in an excellent condition and is currently being restored to its former glory by its present owners. His tomb in the Knights' Cathedral St John's Co-Cathedral is considered the largest and most sumptuous of all the Grand Masters' tombs.