As a boy, a group of Oromo fighters 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 Mugessa, the mother of Sarsa Dengel and widow of Emperor Menas. His mother was Ḥamelmal Wärq, who conceived Susenyos with Fasilidas while married to another man.
In 1590s, Susenyos was perceived as one of the potential successors to the throne, as Emperor Sarsa Dengel's sons were very young. In order to eliminate him from the competition, Empress Maryam Sena had Susenyos exiled, but Susenyos managed to escape and find refuge amongst the Oromo. At the death of his one-time ally, Emperor Za Dengel, he was proclaimed his successor and returned to the realm, although the fight against Emperor Yaqob continued.
Susenyos became Emperor following the defeat of first
Za Sellase, then on 10 March 1607 Yaqob at the
Battle of Gol in southern Gojjam. After his defeat, Za Sellase became a supporter of Susenyos, but fell out with Susenyos early in his reign, and was imprisoned on an amba in Guzamn. After a year, Za Sellase managed to escape and lived as a brigand for a year until he was killed by a peasant, who sent his head to the Emperor.
In 1608, a rebel appeared near Debre Bizen. Because the body of Yaqob had never been found after the Battle of Gol, there had been some doubt that the previous Emperor was truly dead, and a pretender announced that he was the dead Emperor Yaqob. The pretender managed to disguise the fact he did not resemble Yaqob by keeping part of his face covered, claiming that he had suffered grievous wounds to his teeth and face from the battle. The governor of Tigray,
Sela Krestos, eventually heard of the revolt, and not trusting the loyalty of a general levy of troops struck against the rebel with his own household and the descendants of the Portuguese soldiers who had followed Cristóvão da Gama (son of the legendary Portuguese explorer Vasco da Gama) into Ethiopia. Despite their defeating the rebels three different times, the pretender managed to escape each battle to hide in the mountains of Hamasien.
Meanwhile, Emperor Susenyos was preoccupied with raiding parties of the Oromo. An initial encounter with the
Marawa Oromo near the upper course of the Reb River ended in a defeat for the Ethiopians; Susenyos rallied his men and made a second attack which scattered the Oromo. The Marawa allied with other Oromo, and the united force entered Begemder to avenge their defeat. Upon hearing of this, the Emperor responded by summoning his son-in-law Qegnazmach Julius and Kifla Krestos to join him with their troops, and defeated the raiders at
Ebenat on 17 January 1608. According to James Bruce, the Royal Chronicle of Susenyos reports 12,000 Oromo were killed while only 400 on the Emperor's side were lost. With the Oromo threat dealt with, Susenyos now could turn his attention to Yaqob the pretender; he marched to Axum by way of the
Waldebba, where he was formally crowned Emperor 18 March 1608, in a ceremony described by João Gabriel, the captain of the Portuguese in Ethiopia. Despite this act legitimizing his rule, Susenyos had no luck capturing the pretender, and was forced to leave the task to his servant Amsala Krestos. Amsala Krestos induced two brothers who had joined the rebellion to assassinate Yaqob the pretender, who then sent the dead man's head to Susenyos. Without a scarf obscuring his features, writes Bruce, "it now appeared, that he had neither scars in his face, broken jaw, nor loss of teeth; but the covering was intending only to conceal the little resemblance he bore to king Jacob, slain, as we said before, at the battle of Lebart."
In 1615, he conquered and annexed the Kingdom of Fazughli into the Ethiopian Empire, on the Sennar Sultanate borderlands. The emperor sent priests to renew the Orthodox Christianity of the province, though the missionaries seem to have become mired in doctrinal disputes, and their accomplishments were limited 
According to his Royal Chronicle, Susenyos made his power felt along his western frontier from Fazogli, or Fazughli, north to Suakin.