He was ordained priest in 1849 after studies at Saint-Sulpice, Paris. He taught at the Sorbonne but resigned his professorship to become director of the Society for the Promotion of Education in the Near East (Oeuvre des Écoles d'Orient), through which he raised aid for those Maronites (Lebanese Christians) who had survived the massacre of 1860 led by the Druzes, a Middle Eastern people whose religion is derived from Islām. His tour of Lebanon at that time inspired his missionary plans.

Consecrated bishop of Nancy, Fr., in 1863, he was appointed archbishop of Algiers in 1867. With the support of Emperor Napoleon III of France, Lavigerie overrode the local government's disapproval of missionary work among Algerian Muslims and established villages for orphans. He founded the Society of Missionaries of Africa in 1868 for work in northern Algeria, and by 1878 he had encouraged the society to extend its missions to equatorial Africa. Expanding his activities into Tunisia, he was named cardinal in 1882 by Pope Leo XIII, who in 1884 made him primate of Africa and archbishop of the restored see of Carthage.

He had always opposed slavery, and he spent his last years organizing antislavery societies to protect the people of central Africa. Three years after his death, the Society of Missionaries was working in West Africa, and the society was finally approved by Pope St. Pius X in 1908.