It was originally built in the early 17th century as a country villa for Antoine de Paule, a knight of the Order of St. John.

In around 1600, Antoine de Paule, a knight of the Order of St. John from the Langue of Provence, acquired a piece of land in Attard and built a country villa.

[3] De Paule planned the villa on generous proportions to provide accommodation for his guests and his large domestic staff which included cooks, food tasters, torch bearers, pantry boys, wig makers, a winder of the clocks, physicians, as well as a baker to make black bread for feeding his hunting dogs.

[1] During the French occupation of Malta and the subsequent Maltese uprising, the palace was the meeting place of the rebel National Assembly, which first met on 11 February 1799.

Some structural changes were made during British rule, including a reduction of the height of the tower after it was hit by lightning in 1819,[5] and the addition of a balustraded walk around the main courtyard.

[11][12] San Anton Palace is a two-storey building, with a high square tower which has panoramic views of the surrounding area.

It was later converted to a Russian Orthodox chapel to accommodate Grand Duchess Maria Alexandrovna of Russia, the wife of Alfred, Duke of Saxe-Coburg and Gotha.

[14] San Anton Gardens are laid out in a formal manner, with graceful walkways, sculptures, ornamental ponds with ducks, swans and turtles, and a small aviary.

[16] The Malta Community Chest Fund, a charitable organization headed by the president, also occasionally holds fund-raising events at the palace.

[18] San Anton Palace and its gardens probably influenced subsequent Grand Masters to build their own residences and gardens, such as Giovanni Paolo Lascaris, who built Ġnien is-Sultan in Valletta,[19] and António Manoel de Vilhena, who built Casa Leoni in Santa Venera.