Settlement in Vác dating as far back as the Roman Empire has been found. The origin of its name is debated. One hypothesis says that the name comes from a Hungarian tribal name "Vath". Another theory says the name comes from czecho-slovak personal name Vac (Vác), which is the diminutive form of Václav.

It has been the seat of a Roman Catholic bishopric since the 11th century. Bishops from the Roman Catholic Diocese of Vác were influential within the Kingdom of Hungary, with many serving as chancellors or later becoming archbishops.

On 17 March 1241, due to the attack of Mongols the population was slaughtered and Mongols set up camp there. After the departure of the Mongols, Vác was rebuilt and German colonists were invited to the town.

The town was conquered by the Ottoman Empire in 1541. During the Habsburg Monarchy's wars against the Ottomans, the Austrians won victories against the Turks at Vác in 1597 and in 1684. After the Great Turkish War, Vác was rebuilt and repopulated. This re-population was both spontaneous and planned. According to the Truce of Zsitvatörök, Habsburg control of the fortress at Vác (also known as Vacz) was maintained, and its repair was sanctioned.

During the Hungarian Revolution and War of Independence of 1848-49, the Honvédség routed the Austrian forces stationed in the city after a major battle (April 10, 1849); the Second Battle of Vác ended in Russian victory (July 17).

During World War II, Vác was captured on 8 December 1944 by Soviet troops of the 2nd Ukrainian Front in the course of the Budapest Offensive.