Catholicism, as both an institution and a culture of popular beliefs, rituals, and values, has played an important role in the formation of racial boundaries in American society. The logic of race and its inherent function as a mechanism of social power, in turn, profoundly shaped Catholic thought and practice throughout the church’s own 400-year formation in America. Beginning with colonization of the New World, Catholicism defined and institutionalized racial difference in ways that both adhered to and challenged the dominant Anglo-American conceptions of whiteness as a critical measure of social belonging. Early Catholic missions abetted European colonialism by codifying Africans and Native Americans as cultural and moral “others.” Following a “national parish” system, institutional growth from the mid-19th to the mid-20th century sorted various European “races” and created spaces for resisting Anglo-American discrimination. The creation of a separate and singular mission for all “non-white” communities nonetheless reflected Catholic acquiescence to an American racial binary. Intra-Catholic challenges to racialist organization struggled to gain traction until the mid-20th century. As second- and third-generation European immigrants began asserting white status in American society, Catholic understandings of sacred space, which infused white resistance to neighborhood integration with religious urgency, and hierarchical ordering of moral authority within an institution that historically excluded non-whites from positions of influence created significant barriers to Catholic interracialism. The influence of the civil rights movement and the structural transformation of both Catholic life and urban communities where non-whites lived nonetheless prompted new efforts to enlist Catholic teaching and community resources into ongoing struggles against racial oppression. Debates over the meaning of race and American society and social policy continue to draw upon competing histories of the American Catholic experience.