Al-Kindi was born in Kufa to an aristocratic family of the Arabian tribe of the Kinda, descended from the chieftain al-Ashath ibn Qays, a contemporary of Muhammad. The family belonged to the most prominent families of the tribal nobility of Kufa in the early Islamic period, until it lost much of its power following the revolt of Abd al-Rahman ibn Muhammad ibn al-Ashath. His father Ishaq was the governor of Basra and al-Kindi received his preliminary education there. He later went to complete his studies in Baghdad, where he was patronized by the Abbasid caliphs al-Mamun () and al-Mutasim (). On account of his learning and aptitude for study, al-Ma'mun appointed him to the House of Wisdom, a recently established center for the translation of Greek philosophical and scientific texts, in Baghdad. He was also well known for his beautiful calligraphy, and at one point was employed as a calligrapher by Caliph al-Mutawakkil (). 
When al-Mamun died, his brother, al-Mutasim became caliph. Al-Kindis position would be enhanced under al-Mutasim, who appointed him as a tutor to his son. But on the accession of al-Wathiq (), and especially of al-Mutawakkil, al-Kindis star waned.  There are various theories concerning this: some attribute al-Kindis downfall to scholarly rivalries at the House of Wisdom; others refer to al-Mutawakkils often violent persecution of unorthodox Muslims (as well as of non-Muslims); at one point al-Kindi was beaten and his library temporarily confiscated. Henry Corbin, an authority on Islamic studies, says that in 873, al-Kindi died "a lonely man", in Baghdad during the reign of al-Mutamid (). 
After his death, al-Kindis philosophical works quickly fell into obscurity; many were lost even to later Islamic scholars and historians. Felix Klein-Franke suggests several reasons for this: aside from the militant orthodoxy of al-Mutawakkil, the Mongols also destroyed countless libraries during their invasion of Persia and Mesopotamia. However, he says the most probable cause of this was that his writings never found popularity amongst subsequent influential philosophers such as al-Farabi and Avicenna, who ultimately overshadowed him. His philosophical career peaked under al-Mutasim, to whom al-Kindi dedicated his most famous work, On First Philosophy, and whose son Ahmad was tutored by al-Kindi.