He was born in Medina on April 20, 702. His father was the grandson of Imam Husayn, and thus great grandson of Muhammad. His mother (Umm e Farwah) was the great grandaughter of Abu Bakr. As a child, Jafar studied under his grandfather, Ali Zain al Abidin (the fourth Shia Imam). After his grandfather's death, he studied under and accompanied his father, Muhammad al-Baqir (the fifth Shia Imam). Jafar's father would die in 743, passing the title of Imam on to his son. As the son of two prominent Imams, and descendents of Muhammad, he would become well versed in Islamic sciences including Hadith, Sunnah, and the Quran.
Shortly after Jafar became Imam, Jafar's uncle, Zaid bin Ali led a rebellion against the Umayyads. Jafar did not participate, but many of his kinsmen, including his uncle were killed, and others were punished. Despite the violence surrounding him, Jafar continued to stay out of politics and concentrated on teaching others. He was very well respected and well-known, and many people from across the Islamic empire would come to study under him. In addition to his knowledge of Islamic sciences, Jafar was well educated in natural sciences and mathematics. Among his most famous students were the founders of two Sunni schools of jurisprudence: Abu Hanifa and Malik ibn Anas. Jafar was known for his liberal views on learning, and was keen to debate with scholars of different faiths and of different beliefs.
Despite Jafar's abstainment from politics, he was often harassed by the new Abbasid rulers and he was even imprisoned a few times. The reason for this persecution was due to Jafar's popularity, and his standing as a descendent of Muhammad. The rulers feared that he would be able to mobilize against them, and as such they thought it keen to keep him in check. He would eventually die from poisoning on December 4, 765. He is buried in Medina, in the famous Jannat al-Baqi cemetary.
The split between Twelver Shias and the Ismailis (Seveners), originated with the son of Jafar. The first son of Jafar, Ismail bin Jafar died before Jafar. The split occured between those who felt that Ismail was the rightfull sucessor to Jafar, and the true seventh imam, and those who felt that Ismail's brother, and one of Jafar's younger sons, Musa al Kazim was the rightful sucessor to Jafar. It is from Ismail that the Ismailis derive their name. The Aga Khans are descendents of Ismail.