The Mississippi River Valley at the turn of the nineteenth century was a site of intense religious competition. Far from Christian institutional centers, and inhabited by an eclectic mix of races, nationalities, religious confessions, and language groups, the region posed a threat to eastern America's self-understanding as a Protestant nation. To claim and control the Mississippi Valley, Protestant evangelicals sent missionaries to institute their doctrines and practices among the French, Creole, African, Native American, and Anglo-American populace. But their opponents had a head start. Catholic missionaries had been proselytizing the Mississippi Valley for a century, and at the sign of a Protestant invasion, Catholic leaders injected more material, financial, and human resources into the region. “Holy Waters” recovers the neglected story of this dynamic religious contest. Drawing on missionary reports, diaries, letters, emigrant guides, and institutional records, “Holy Waters” examines the religious proclivities and choices of the inhabitants who navigated contending efforts to corral them into faithfulness. By highlighting Catholic and animist vitality and exposing the intense and complicated contest for religious dominance in the region, “Holy Waters” challenges the narrative of inevitable Protestant evangelical victory and expands the story of American religious history. The study also has the potential to prompt ethical reflection among contemporary leaders engaged in revitalizing Christian institutions in the U.S. Its examination of the deep roots of the deployment of the religious Other to motivate Catholic and Protestant institution building can inform consideration of the ethics of twenty-first-century uses of Islam to buttress American Christianity, while its assessment of the historical development of American Protestant notions of national identity and national destiny invites reflection on the sources of contemporary political fissures.