Founded in 1978 by north St. Louis pastors and lay Catholics, the center was a pioneering effort to intentionally uplift Black Catholic voices. Originally situated in the Penrose neighborhood, the physical center relocated to the St. Rita Church campus in Vinita Park. Administratively, the center merged with the archdiocese's Office of Racial Harmony & Black Catholic Ministries to streamline its community outreach and equity initiatives.

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The St. Charles Lwanga Center is named after a Ugandan saint martyred with his companions for his faith, it serves as a central hub for spiritual formation and advocacy within the African American Catholic community.