A member of the lesser nobility, Werbőczi was commissioned by King Vladislas II to collect the customary and statute law of the Hungarian kingdom. His resulting work, the famous Tripartitum (1514), most notably proclaimed the complete equality of all nobles, both great and small, and stressed the rights of the aristocracy at the expense of royal sovereignty. It also reinforced the servile status of the peasantry, thus leading to a further deterioration of their condition. In effect, the Tripartitum virtually identified aristocratic interests with the nation's legal personality.

During the reign of Vladislas' young son Louis, Werbőczi served on several diplomatic missions to obtain assistance against the Turks and in 1525 was elected palatine (imperial governor), a position he was, however, soon forced to resign. Following King Louis's death during the disastrous rout of the Hungarians by the Turks at Mohács (August 1526), Werbőczi supported the native claimant to the royal succession, János Zápolya (later King John), against the Habsburg Ferdinand I. In 1541 he advised that Buda be ceded to the Turks, and in the Turkish administration he rose to the rank of chief justice. He was, however, soon poisoned by the Pasha of Buda.