Some Hungarian nobles proposed that Ferdinand, who was the ruler of neighboring Austria and tied to Louis II's family by marriage, be King of Hungary, citing previous agreements that the Habsburgs would take the Hungarian throne if Louis died without heirs. However, other nobles turned to the nobleman John Zápolya, who was being supported by Suleiman. Under Charles V and his brother Ferdinand I, the Habsburgs reoccupied Buda and took possession of Hungary.

Zápolya refused to give up his claims to the Hungarian throne and therefore appealed to Suleiman for recognition in return for tribute. Suleiman accepted Zápolya as his vassal in February and in May 1529 Suleiman personally embarked on his campaign.On 26–27 August Suleiman had Buda encircled and the siege began. The walls were destroyed by intensive cannon and gun fire of the Ottomans between 5 and 7 September. The military preparedness, uninterrupted attacks and physical and psychological destruction that was caused by the Ottoman artillery had the desired effect. The German mercenaries surrendered and ceded the castle to the Ottomans on 8 September. John Zápolya was installed in Buda as a vassal of Suleiman.After the defeat of Ferdinand his supporters were promised safe passage from the town, however the Ottoman troops slaughtered them outside of the city walls.