Cholera affected millions of people as it spread from its point of origin in northeastern India and marched along trade routes in the late 1820s and into Europe in the early 1830s. Many Americans, particularly those in cities on the eastern seaboard, watched it rampage across Europe with trepidation. Quarantines had failed to stop the spread of the disease, and American observers soon came to believe that the Atlantic Ocean could only delay, but not completely halt, its inevitable arrival.

Still, certain facts about American life in the early 1830s reassured the fearful, convincing many that cholera's impact in the United States would be less severe than it had been in Europe. The hardest hit areas of Europe were city slums, where poverty and vice (rather than unsanitary living conditions) were assumed to predispose victims to catching cholera. The United States in 1832 was still predominantly rural, and the poverty that typified Europe's cities was contained in smaller urban slums in America. Should cholera hit, many Americans believed its impact would be limited by American demographics. Further, popular beliefs about the vigorous physical constitution of Americans, commonly invoked in Jacksonian America, reinforced the general sense that cholera's impact in the United States would be limited.

Cholera reached North America in June 1832, first appearing in Quebec, Canada, on June 6, and then traveling down the St. Lawrence to the Hudson River. Citizens of New York City were well aware of its approach, and despite proclamations that the well-born had little to fear from cholera, those who could afford to leave the city began to travel to rural areas on Long Island and in New Jersey. The disease finally entered New York City on June 26, when an Irishman named Fitzgerald became violently ill. He survived, but his two daughters and his wife were dead from cholera within a few days; over the next two weeks the number of reported cholera cases grew dramatically.

Cholera proceeded to kill 3,500 New York City residents in two months, the majority of whom were residents of the city's slums. This fact alone confirmed for many Americans the notion that the disease was a scourge visited upon poor folks who damaged themselves with drink and thus made themselves more susceptible to disease. Most commentators on the outbreak viewed cholera in such moralistic terms rather than as a general public health problem. While the outbreak did spur some debate over public sanitation, such discussion often implied cholera should be blamed on its victims rather than on their environment.

While it was undeniable that the poor — mostly Irish and black — were most susceptible to cholera, debate emerged around the question of whether or not the disease was a divine punishment for sin. Science and religion in the 1830s were closely related in the years before Charles Darwin developed the theory of evolution, and medicine regularly mixed morality with knowledge. Newspapers reporting on the progress of the disease in Europe described its "lewd" victims, and the well-to do who lost family members to cholera did all they could to keep secret the cause of death. Cholera, once in New York, was even lauded by some city leaders for doing good and necessary work by thinning out the poor and debauched. Cholera was viewed in many circles as a great teacher, a reminder of God's power and of what the end-result of an intemperate life would be.

Some Americans took a less harsh stance. Many argued that man could not pretend to know God's true intentions, while others blamed business leaders and politicians for allowing slums and poverty to expand. For them, the fact that cholera could affect America at all revealed how truly unequal a society was emerging. Still others used the cholera outbreak for political reasons: nativists, for example, pointed to cholera's prevalence among immigrants as a reason to restrict entry.