Manoel de Almeida, a Jesuit who lived in Ethiopia during Susenyos' reign, described him as "tall, with the features of a man of quality, large handsome eyes, pointed nose and an ample and well groomed beard. He was wearing a tunic of crimson velvet down to the knee, breeches of the Moorish style, a sash or girdle of many large pieces of fine gold, and an outer coat of damask of the same colour, like a capelhar
As a boy, a group of marauding Oromo captured him and his father, holding them captive for over a year until they were rescued by the Dejazmach Assebo. Upon his rescue, he went to live with Queen Admas Mogasa, the mother of Sarsa Dengel and widow of Emperor Menas.
In 1590s, Susenyos was perceived as one of potential successors, as Emperor Sarsa Dengel's sons were very young. At the death of his one-time ally, Emperor Za Dengel, he was proclaimed his successor, although the fight against Emperor Yaqob continued.
Susenyos became ruler following the defeat of first Za Sellase, then Yaqob at the Battle of Gol, located in southern Gojjam, in 1607. However, he delayed being crowned until March 18 1608, in a ceremony at Axum described by Joao Gabriel, the captain of the Portuguese in Ethiopia. Because the body of Yaqob had never been found after the Battle of Gol, for the first few years of his reign Susenyos was troubled by revolts from a number of men claiming to be the dead king.
Susenyos campaigned against the Agaw in the north, the encroaching Oromo in the south, and is said in his Royal Chronicle to have made his power felt along his western frontier from Fazogli north to Suakin.
He was interested in Catholicism, in part due to Pedro Páez' persuasion, but also hoping for military help from Portugal and Spain (in union at the time of Susenyo's reign). Some decades earlier, in 1541, Christopher da Gama (son of the legendary Portuguese explorer Vasco da Gama) had been in charge of a military expedition to save the Ethiopian emperor Gelawdewos from the onslaught of Ahmed Gragn, a Muslim Imam who almost destroyed the existence of the Ethiopian state. Susenyos hoped to receive a new contingent of well-armed European soldiers, this time against another enemy, the Oromo who were invading from the south, and to put down constant internal rebellion. He showed the Jesuit missionaries his favor by a number of land grants, most importantly those at Gorgora, located on a peninsula on the northern shore of Lake Tana.
In 1613, Susenyos sent a mission heading for Madrid and Rome, led by Fr. Antonio Fernandes. The plan was to head south, in an attempt to reach Malindi, a port on the Indian Ocean in what is Kenya today, hoping to break through the effective blockade that the Ottoman conquests had created around the Ethiopian empire by sailing all the way around the southern tip of Africa. However, they failed to reach Malindi, due to delays caused by local Christians hostile to the mission.
Despite several letters from Susenyos to the King of Spain (and Portugal), Philip III, asking for military help, no Spanish or Portuguese soldiers ever arrived. Even so, Susenyos at last converted to Catholicism in 1622 in a public ceremony, and separated himself from all of his wives and concubines except for his first wife. However, the tolerant and sensitive Pedro Paez died soon afterwards, and his replacement Alfonso Mendez, who arrived at Massawa on January 24, 1624, proved to be haughty and less tolerant of traditional practices. Strife and rebellions over the enforced changes began within days of Mendez' public ceremony in 1626, where he proclaimed the primacy of Rome and condemned local practices, suppressing even the use of the Ethiopian calendar.
In 1630, the Viceroy of Begemder, Sarsa Krestos, proclaimed Susenyos's son Fasilides emperor; Sarsa Krestos was promptly captured and hanged. Two years later, Susenyos's brother Malta Krestos revolted in Lasta, which was put down at the cost of 8,000 lives. This purposeless loss of life depressed Susenyos, and on returning to his palace at Dankaz, he granted his subjects freedom of worship, in effect restoring the traditional Ethiopian Church.
He ended his reign by abdicating in favor of his son, Fasilides. He was buried at the church of Genneta Iyasus.