The Common Council, the legislative branch of New York City government, appointed a standing Board of Health in 1805 after a series of yellow fever epidemics had ravaged the city over the previous decade. The Board of Health tended to act only in response to the outbreak of disease, setting aside barracks for the sick, establishing quarantines, and gathering information to report to the Common Council. Despite its permanence, the activity of the board ebbed and flowed with the presence of epidemic disease in the city. After the yellow fever outbreak of 1822, the board did little for the following decade beyond instituting the occasional quarantine.

As cholera swept through Europe, the board foresaw the responsibility it would face if the disease jumped the Atlantic. The board had established a quarantine during the winter months, but pressure through the Common Council from city merchants eager to receive their goods limited its effectiveness. When news of the disease's presence in Montreal reached the city, the board met and established a system employing councilmen as "health wardens" for each of their wards who would enact the policies of the board. The board, which had no physicians, also set up a Special Medical Council consisting of seven prominent doctors to advise and guide its response.

The board’s first order of business was to secure emergency money from the Common Council. It then established five temporary hospitals to care for cholera patients. The next step was to cleanse the streets, a step meant to "purify" the city to limit cholera's sticking power. Then the board, believing the overpopulation of the slums contributed to the foul air that propagated cholera, established a Committee to Provide Suitable Accommodations for the Destitute Poor, which oversaw the dispersal of residents of the city's slums to several poor-houses. The condition of these institutions was usually the same or even worse than the housing left behind by tenants and, even though private philanthropic organizations assisted with feeding and clothing the displaced poor, their suffering continued. Most commerce in the city ground to a halt, as the prosperous had evacuated and fear gripped those who remained. This added to the problems of laborers whose ability to support their families depended on the availability of regular work. The Board of Health also acted as a repository for complaints about the city's response to the epidemic. The most gruesome concerned the inadequate disposal of corpses at the city cemetery, Potter's Field, and compelled the board to lay down specific requirements for how bodies should be buried.

When cholera was in full swing in the city, the Board of Health was quite active, performing admirably under dire circumstances. Its response also can be seen as one of the earliest, large-scale acts of urban municipal action. Yet, in part due to the lack of knowledge about the disease, and also to the reluctance of the city's leaders to act until cholera bore down upon Manhattan, the responses were less effective than they could have been. Cholera claimed more than 3500 victims as it ran its course in Manhattan alone during the summer of 1832. But perhaps the most crucial failure of the Board of Health was that the progress it made during the 1832 epidemic proved transitory. By the middle of the decade, the board's activities were once again minimal, and would not be expanded again until cholera struck the city seventeen years later.