His father's supporters (Arabic: شـيـعـة عـلي, Shi‘at ‘Ali) in Al-Kufah gave their allegiance to him. However, he told them he was still bound to the peace treaty between Al-Hasan and Muawiyah I and they should wait until Mu‘awiyah's death. Later, Al-Husain did not accept the request of Mu‘awiyah for the succession of his son, Yazid I, and considered this action a breach of the Hasan–Muawiya treaty.
When Mu‘awiyah died in 680 ACE, Al-Husayn refused to pledge allegiance to Yazid, who had just been appointed as Umayyad caliph by Mu‘awiyah, because the Umayyads were reportedly an oppressive and religiously misguided regime. He insisted on his legitimacy based on his own special position as a direct descendant of Muhammad and his legitimate legatees. As a consequence, he left Medina, his home town, to take refuge in Mecca in 60 AH. There, the people of Al-Kufah sent letters to him, asking his help and pledging their allegiance to him. So he travelled towards Al-Kufah, but, at a place near it known as Karbala’, his caravan was intercepted by Yazid's army. He was killed and beheaded in the Battle of Karbala’ on 10 October 680 (10 Muḥarram 61) by Shimr Ibn Thil-Jawshan, along with most of his family and companions. Anger at Al-Husayn's death was turned into a rallying cry that helped undermine the Umayyad caliphate's legitimacy, and ultimately overthrow it by the ‘Abbasid Revolution.