Throughout the nineteenth century, anti-Catholic prejudice manifested itself in various popular, political, and violent forms. Protestants and other non-Catholics viewed the church as authoritarian and anti-individualistic and therefore un-American and un-democratic. While few Roman Catholics lived in America prior to the Revolutionary War, by the time the Civil War broke out in 1860, Roman Catholicism was the largest Christian denomination. The significant growth of Roman Catholicism in the U.S. was due to immigration, primarily from Ireland and Germany in the early nineteenth century and from southeastern Europe in the second half of the nineteenth century.

In the early nineteenth century, anti-Catholic prejudice was mainly popular. Non-Catholics viewed Catholics, particularly priests and nuns, as living secret lives and made them the focus of salacious exposes, like Awful Disclosures of Maria Monk, or, The Hidden Secrets of a Nun's Life in a Convent Exposed (1836). In addition, non-Catholics also violently targeted churches and convents. One of the most famous incidents of this popular form of anti-Catholic sentiment expression occurred on the night of August 11, 1834. Non-Catholic rioters looted and burned the Ursuline Convent of Mount Benedict in Charlestown, Massachusetts, where Catholic nuns taught predominantly wealthy Protestant girls. Anti-Catholic violence also erupted in Philadelphia when thirteen people were killed in riots in 1835. Activities by the American Nativist Party in Kensington, Pennsylvania, in 1844 also sparked anti-Catholic riots.

By the mid-nineteenth century popular forms of anti-Catholicism dissipated while more politically organized anti-Catholicism emerged. Issues of contention revolved less around the lives of priests and nuns and more so around parochial schools and the influence of the Church hierarchy on the political decisions of the laity. In the 1850s, the American Party, also known as the National Americans or the Know-Nothing Party, was partly founded on an anti-Catholic platform. While the American Party did gain some political headway during the decade, the divisive issue of slavery and the coming of the Civil War prevented it from becoming a major political party. The American Protective Association (APA) was the major anti-Catholic organization to emerge in the second half of the nineteenth century. Founded in 1887, the APA particularly sought to prevent Catholics from gaining political office. The resurgence of the Ku Klux Klan after World War I was one of the last organized forms of anti-Catholicism.