Yeshaq's reign was marked by a revolt of the Beta Israel. In response, the Emperor marched into Wogera, where he defeated the rebels at Kossoge, thereby ending the revolt. He also had the church Debre Yeshaq built there to commemorate his victory. Yeshaq also invaded the Shanqella region beyond Agawmeder, and to the southeast he fought against the sons of Sa'ad ad-Din II who returned from exile in Arabia.
During Yeshaq's reign, according to the Islamic historian al-Maqrizi, a group of Mameluks led by al-Tabingha made their way to Ethiopia, where he taught Yeshaq's soldiers how to make flame-throwers and fight with swords. About the same time another Egyptian visitor, a Copt, "reorganized the kingdom," according to al-Maqrizi, "and collected so much wealth for the Hati [the Emperor] that he enjoyed the king's authority." This unnamed Copt also introduced the practice of the Emperor dressing in "splendid" clothes and carrying a cross, which made him stand out from his subjects. Further, G.W.B. Huntingford suggests that it was during Yeshaq's reign that the rulers of Ethiopia ceased having permanent capitals; instead, their courts were held in their encampments as they progressed around their realm.
Yeshaq made the earliest known contact from post-Axumite Ethiopia to a European ruler. He sent a letter by two dignitaries to Alfonso V of Aragon, which reached the king in 1428, proposing an alliance against the Muslims and would be sealed by a dual marriage, that would require the Infante Don Pedro to bring a group of artisans to Ethiopia, where he would marry Yeshaq's daughter. It is not clear how or if Alfonso responded to this letter, although in a letter that reached Yeshaq's successor Zara Yaqob in 1450, Alfonso wrote that he would be happy to send artisans to Ethiopia if their safe arrival could be guaranteed, for on a previous occasion a party of 13 of his subjects travelling to Ethiopia had all perished.
A notable example of Ethiopian literature that has survived from this period is a panegyric addressed to Yeshaq, which Enrico Cerulli singled out as a gem of Ethiopian poetry.
Tadesse Tamrat believes that the primary sources mask Yeshaq's death in battle against the Muslims. E. A. Wallis Budge states that he was assassinated, and "buried in Tadbaba Maryam".