Al-Mundhir was the son of 'Amr ibn Khunays from the Banu Sa'ida clan of the Khazraj. His lineage is traced back through Lawdhan ibn 'Abd Wudd to the progenitor of the Khazraj tribe. His mother was Hind bint al-Mundhir from the Banu Salama clan. Notably, Al-Mundhir was literate and capable of writing in Arabic prior to the advent of Islam, a skill that was relatively rare in Arabia at the time.
Al-Mundhir was among the early converts to Islam in Medina (then Yathrib). Following his conversion, he partnered with Sa'd ibn 'Ubada and Abu Dujana to destroy the idols belonging to the Banu Sa'ida clan. He was later selected as one of the twelve Nuqaba (tribal representatives) during the Second pledge at al-Aqabah, where he pledged his life and loyalty to Muhammad. After the Hijra, Muhammad established a formal bond of brotherhood between Al-Mundhir and the Muhajir Abu Dharr al-Ghifari
Al-Mundhir participated in the Battle of Badr in 624 CE, the first major engagement between the Muslims and the Quraysh. During the Battle of Uhud the following year, he was entrusted by Muhammad with the command of the infantry's left wing, demonstrating his high standing within the early Muslim military hierarchy.
In late 625 CE (4 AH), Muhammad dispatched Al-Mundhir at the head of 70 riders, primarily consisting of the Qurra (Quran reciters), to Najd. The mission was initiated following a request from the chieftain Abu Bara, who had provided a guarantee of safety (amān) for the Muslim emissaries.
However, upon reaching the well of Bi'r Ma'una, the party was betrayed and surrounded by the tribes of Banu Sulaym, led by Amir ibn al-Tufayl. Most of the Muslims were killed in the initial onslaught. Al-Mundhir, as the group's commander, was the last to survive. According to tradition, the attackers offered him protection if he surrendered, but he refused, declaring that he would not accept the security of a polytheist. He fought until he was martyred. It was due to his unwavering resolve to face death in this engagement that he earned the title A'naq al-Mawt ("The one who hastens to death").