In 1403, after learning about his father's death in captivity, began to struggle for the vacant throne against his brothers Mehmet Çelebi, Musa Çelebi, and Süleyman Çelebi. He fought against Musa to gain control of Bursa, the Anatolian capital of the empire. He defeated Musa and won control of a part of Anatolian territory of the empire. But the European territory, Rumeli, was under the control of Süleyman and the east part of Anatolian territory was under the control of Mehmet (the future Mehmet I). Feeling his lands to be fragile situated between his brothers' on both sides, he signed a treaty of friendship with the Byzantine emperor Manuel II Palaiologos and refused Mehmet's suggestion to partition the Anatolian part of the empire with him, on the grounds that he was the older brother and was entitled the entirety of the territory. But following this refusal, he was defeated by Mehmet in the Battle of Ulubat in 1405. In this battle, he also lost his vizier Timurtaş, who was an experienced statesman. He escaped to Rumeli over Byzantine territories. He married the daughter of Ioannes Tuntares, the granddaughter of Manuel II Palaiologos.
He met with Süleyman, who supported his cause in Anatolia. With fresh troops provided by Süleyman, he returned to Anatolia and tried to recapture Bursa. Although he failed, allying himself with the Anatolian beyliks, which his father Beyazıt I had captured but which had regained independence after Beyazıt's defeat at the Battle of Ankara, he continued to fight against Mehmet. However, after a series of defeats and the betrayal of his allies, and İsa gave up the war for the throne.
According to historian Joseph von Hammer, after losing the struggle, İsa went into hiding. According to other sources, however, he was spotted in a public bath (Turkish: hamam) in Eskişehir and killed by Mehmet's partisans in 1406.