Al-Amin, seeing that most of the army was with Al-Ma'mun, tried to appease him. Al-Ma'mun appointed Harthama bin 'Ayn to Egypt in the year 190 AH. However, this did not bring him satisfaction, as Harthama did not deviate from Al-Ma'mun's loyalty.

Al-Amin sent an army of forty thousand men to Khurasan in the year 191 AH to fight Al-Ma'mun. Tahir bin Al-Husayn, leading Al-Ma'mun's troops, met them and routed them. Al-Ma'mun was thus completely victorious in the eyes of Muslims, and the people of Khurasan strengthened their support for him. Harthama then turned to Egypt. When Al-Amin saw this, he appointed Jabir bin Al-Ash'ath to Egypt in the same year.

Harthama bin 'Ayn built a fortress on the slopes of Mount Muqattam, near the current Citadel of Cairo. After Jabir bin Al-Ash'ath was appointed to Egypt, Al-Amin's strength increased, and he felt confident of victory over his brother. He gathered an army of forty thousand men to fight him. Al-Ma'mun, on the other hand, sent another army from another direction under the command of Abdullah bin Humayd bin Qahtaba, whose father had been governor of Egypt during the reign of Al-Mahdi. Tahir bin Al-Husayn, however, did not engage these armies but instead advanced to Ahwaz.

Jabir bin Al-Ash'ath was in charge of Egypt. When the conflict between Al-Amin and Al-Ma'mun escalated, Al-Sari bin Al-Hasan, in anger on behalf of Al-Ma'mun, called upon the people to depose Al-Amin. They responded and pledged allegiance to Al-Ma'mun in Jumada al-Akhirah of the year 191 AH. In Baghdad, Al-Husayn bin 'Ubayd, one of his commanders, called upon the people to depose Al-Amin and pledge allegiance to Al-Ma'mun. They responded and pledged allegiance in Rajab of the same year.

Al-'Abbas bin Musa sided with Al-Amin, and his mother Zubaida and her children were imprisoned and shackled. Al-Amin, through some intermediaries, managed to escape and reclaim the caliphate, and those in Baghdad pledged allegiance to him. Al-Ma'mun's caliphate extended to Iraq, Yemen, and Egypt, among other places. He appointed Harthama bin 'Ayn as governor of Khurasan and sent Ubayd bin Muhammad as his deputy.

In the year 193 AH, Tahir bin Al-Husayn and Harthama bin 'Ayn attacked Baghdad and besieged it for nearly a year. The people of Baghdad grew weary and tired of the long siege, and they began to await its end. They saw no solution until Al-Amin was deposed for the second time. Shortly thereafter, he was captured and killed. His head, seal, staff, and cloak were brought to Al-Ma'mun. Al-Amin had only two or three hundred men with him at the time of his death. His reign lasted for four years, seven months, and twenty days. His death brought an end to the fighting and shed blood.