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Melchior-Marie-Joseph de Marion Brésillac was born in 1813 at Castelnaudary, in the Aude department of Languedoc in southern France, to a family of the local nobility. He received a classical and ecclesiastical education and was ordained a priest in 1838 for the Diocese of Carcassonne. After a short period of ministry in France he sought admission to the Paris Foreign Missions Society (Missions Étrangères de Paris), which accepted him in the early 1840s. He was assigned to the Indian missions and reached Pondicherry in 1842. There he studied Tamil and the conditions of a church that served both a small European colonial population and a much larger community of Indian Catholics, among whom caste continued to structure social and even religious life.

Rome divided the Pondicherry vicariate in the mid-1840s and erected the Vicariate Apostolic of Coimbatore, naming Brésillac its first vicar apostolic. He was consecrated bishop in 1846. In Coimbatore he promoted seminaries and the training of Indian priests, and he became increasingly critical of missionary willingness to accept caste separations in worship and church organization. He regarded such practices as incompatible with the Gospel and with the unity of the faithful. His stance isolated him from a number of fellow missionaries of the Paris society, who feared that a rigid rejection of caste custom would destroy the mission. After years of tension he offered his resignation, which the Holy See accepted in the mid-1850s. He left India and returned to France, still determined to serve in the missions but no longer within the Indian vicariates.

In Europe he turned his attention to Africa, then only partly occupied by Catholic missionary institutes. With the encouragement of Propaganda Fide he founded at Lyon, on 8 December 1856, the Society of African Missions, a society of apostolic life whose purpose was the evangelization of the African interior and of coastal regions not already committed to other congregations. He gathered a small group of priests and a coadjutor, Augustin Planque, whom he left in Lyon to form recruits and to administer the society. In 1858 the Holy See assigned to the new institute the Vicariate Apostolic of Sierra Leone, a territory covering much of the Upper Guinea coast. Brésillac accepted the charge and prepared to go himself as the first vicar apostolic.

He sailed for West Africa in 1859 with a handful of companions and landed at Freetown in May of that year. The British colony was in the grip of a yellow fever epidemic. One after another the missionaries fell ill. Brésillac, who had barely begun to organize the mission, contracted the disease and died in Freetown on 25 June 1859, only weeks after his arrival. Almost the entire first expedition perished. The Society of African Missions nevertheless survived in Europe under Planque's direction, later sending new personnel to Dahomey (Benin), Nigeria, and other parts of West Africa, where it became one of the principal Catholic missionary bodies of the region. Brésillac is commemorated as the founder of that society and as a bishop who, both in India and in his African project, insisted on the formation of local clergy and on the rejection of social barriers inside the Church. The Catholic Church has opened his cause of beatification and has declared him Venerable.

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