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The First Islamic civil war, 656–661 CE, followed the assassination of the Caliph Uthman Ibn Affan , continued during the brief caliphate of Ali Ibn Abu Talib , and was ended, on the whole, by Mu'awiya 's assumption of the caliphate. This civil war is often called the Fitna , and regretted as the end of the early unity of the Islam ic Ummah (nation).

In 656 CE, the then caliph, or Muslim leader Uthman Ibn Affan , was murdered by rebellious Muslim soldiers as he sat reading the Qur'an in his home in Medina , in north-western Arabia . Medina fell into chaos and uproar. Citizens flocked to Ali Ibn Abu Talib , the Prophet Muhammad 's cousin and son-in-law, and a respected community leader who had been passed over for the leadership three times since the death of the prophet. Now they urged him to take the caliphate. Initially reluctant due to the circumstances of the caliph's death, he was eventually forced to accept.

Ali then had to fight against numerous challengers to his rule. He fought and defeated Muhammad's widow Aisha at the Battle Of The Camel ; he fought Uthman's kinsman Mu'awiya , the governor of Syria , at the Battle Of Siffin to a stalemate and then lost a controversial arbitration; and he fought his own mutinous soldiers (the first Kharijites ). Large sections of the new empire created in the twenty-four years since Muhammad were lost (due to sereval reasons, unrelated to Ali) and the prophet's followers fled Mecca for Medina.

In 661 CE, Ali was assassinated in the Qibla by a relative of one of the rebel soldiers he had defeated and killed. His last words were "Fuzto wa Rabbil Ka'bah" - meaning "By The Lord of the Ka'bah, I have succeeded".

His son Hasan Ibn Ali briefly assumed his cause, but realized that he could not prevail. He came to an agreement with Mu'awiya, of which various accounts are given. He retired to Medina with a state pension, to live as an Imam, not Caliph, while Mu'awiya assumed control of the empire and founded the Umayyad dynasty of Caliphs.