Mustafa was thirty-nine when he became sultan having spent the previous twenty-seven years in the Cage.  He went on to father eleven children: two boys and nine girls with only one of the boys surviving infancy to become the future sultan Selim III.  He was the first royal prince to have been born since the reign of Ahmet III and the whole city celebrated.

During the first four years of his reign Mustafa built two imperial mosques: Ayazma Camii in Üsküdar on the Asian side of the Bosphorus and Laleli Camii in the old quarter of Istanbul. 

A huge earthquake in 1766 destroyed or damaged many important buildings in Istanbul including the Fatih Camii, the mosque built by Sultan Mehmet Fatih the conqueror of Istanbul.  Mustafa immediately set out to rebuild this mosque complex and it was completed in 1771 although with a very different architectural plan to the original.

The fortunes of the Empire were now very much in decline with Catherine the Great of Russia threatening war.  Despite this the sultan continued to hold the flower fetes instigated by Ahmet III.

Mustafa died of heart failure on 21st January 1774 a week before his fifty-seventh birthday.  The only remaining son of Ahmet III, Abdul Hamit, now succeeded to the throne.