Towards the end of his reign Selīm I had been preparing for a new offensive, but no one could be sure where the blow might fall. Now, in September 1520, the great sultan was dead. As the news became known in Christendom, men felt that a dark shadow had been banished, an imminent peril suddenly dispelled. Sulaimān, the only son of Selīm, was said to be ill-versed in affairs and of a quiet nature, a prince, therefore, who would be little inclined to war. Seldom has prediction been more rash or doomed to swifter disillusionment. In 1521 Sulaimān marched against Hungary.

The campaign had been organised with meticulous care: the beglerbeg of Rumeli moved towards Sabacz, the sultan following with most of his household regiments; the grand vizier Pīrī Pasha, with a strong contingent of janissaries and ample provision of siege guns, made for the main objective, Belgrade, which Mehemmed II had tried but failed to capture in 1456. At the same time the Akinjis rode out in two columns, the one to effect a diversion against Transylvania, the other to devastate the lands between the Sava and the Drava. The fall of Sabacz and Semlin severed the routes leading to the north and west of Belgrade, so that Sulaimān was now free to assail the great fortress. Guns bombarded the walls from an island in the Danube, a fierce assault drove the garrison into the citadel, an Ottoman flotilla, sailing upstream, cut off all relief by water. The end came when dissension broke out between the Hungarians and their Serbian mercenaries, the former wishing to prolong, the latter to abandon the defence. Belgrade surrendered on 29 August 1521.