John Zápolya spouse Isabella Jagiellon
Europe's political balance underwent a major shift in the summer of 1527, when, in a somewhat unplanned operation, mercenary forces of the emperor occupied Rome and drove Pope Clement VII, one of France's principal allies, to capitulate. This development freed Ferdinand – who also acquired the Bohemian throne in late 1526 – from the burden of assisting his brother. By then, Ferdinand had developed a Hungarian policy that was fully in keeping with the interests of his realms. He judged that if Hungary, unable to resist the Ottoman Empire, took action independently of Austria and Bohemia, it might well enter into an alliance with the Ottomans against its western neighbors. It was therefore in the interest of Austria and Bohemia that the Habsburgs gain control of Hungary, by force if necessary.
In July 1527, Ferdinand sent an army of German mercenaries into Hungary. The moment was well chosen, for John Zápolya's forces were tied up in the southern counties of Hungary, where Slavonic peasants, incited by Ferdinand, had rebelled; the revolt was led by the 'Black Man', Jovan Nenad. In one sweep, the pro-Habsburg soldiers captured Buda. John hurriedly redeployed his army, but on 27 September in the Battle of Tarcal (near Tokaj), he suffered a bloody defeat. Based on the earlier election of the Diet at Pozsony, Ferdinand was crowned in the Székesfehérvár Basilica on 3 November 1527.
In 1528 John fled Hungary for Poland, where he stayed with Prince Jan Amor Tarnowski. In 1529 John approached the Ottomans, and agreed to make Hungary a vassal state in return for recognition and support. Sultan Suleiman the Magnificent accepted, and sent Ottoman armies to invade Austria (which included the Siege of Vienna), a war which lasted till 1533. This allowed John to regain his position in Hungary in 1529, by the efforts of Frater George Martinuzzi, despite the association with the Ottomans which tainted him at the time. Martinuzzi became royal treasurer and John's most trusted minister.
In 1533, the Ottomans made peace and ceded western Hungary to Ferdinand. Ferdinand now began to press John for control of the rest. In 1538, by the Treaty of Nagyvárad, John designated Ferdinand to be his successor after his death, as he was childless. However, in late January to early February 1539, he married Isabella Jagiellon, and in 15 July 1540 they had a son, John Sigismund. King John died seven days later in 22 July 1540 in Szászsebes (Sebeş).
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