Fasilides was proclaimed Emperor in 1630 during a revolt led by Sarsa Krestos, but did not actually reach the throne until his father abdicated in 1632. Once he became Emperor, Fasilides immediately restored the official status of the traditional Ethiopian Orthodox Church. He sent for a new abuna from the Patriarch of Alexandria, restoring the ancient relationship that had been allowed to lapse. He confiscated the lands of the Jesuits at Dankaz and elsewhere in the empire, relegating them to Fremona. When he heard that the Portuguese bombarded Mombasa, Fasilides assumed that Afonso Mendes, the Roman Catholic prelate, was behind the act, and banished the remaining Jesuits from his lands. Mendes and most of his followers made their way back to Goa, being robbed or imprisoned several times on the way. In 1665, he ordered the "Books of the Franks" -- the remaining religious writings of the Catholics—burnt.
He is commonly credited with founding the city of Gondar in 1636, establishing it as Ethiopia's capital. Whether or not a community existed here before he made it his capital is unknown. Amongst the buildings he had constructed there are the beginnings of the complex later known as Fasil Ghebbi, as well as some of the earliest of Gondar's fabled 44 churches: Adababay Iyasus, Adababay Tekle Haymanot, Atatami Mikael, Gimjabet Maryam, Fit Mikael, and Fit Abbo. He is also credited with building seven stone bridges in Ethiopia; as a result all old bridges in Ethiopia are often commonly believed to be his work.
The rebellion of the Agaw in Lasta, which had begun under his father, continued into his reign and for the rest of his reign he made regular punitive expeditions into Lasta. The first, in 1637 went badly, for at the Battle of Libo his men panicked before the Agaw assault and their leader, Melka Kristos, entered Fasilides' palace and took the throne for himself. Fasilides quickly recovered and sent for help to Qegnazmach Dimmo, governor of Semien, and his brother Gelawdewos, governor of Begemder. These marched on Melka Kristos, who was still at Libo, where he was killed and his men defeated. The next year Fasilides marched into Lasta; according to James Bruce, the Agaw retreated to their mountain strongholds, and "almost the whole army perished amidst the mountains; great part from famine, but a greater still from cold, a very remarkable circumstance in these latitudes."
Fasilides dispatched an embassy to India in 1664-5 to congratulate Aurangzeb upon his accession to the throne of the Mughal Empire.
In 1666, after his son Dawit rebelled, Fasilides had incarcerated at Wehni, reviving the ancient practice of confining troublesome members of the Imperial family to a mountaintop, as they had once been confined at Amba Geshen.