The Willis–Campbell Act emerged as a significant response to the challenges posed by Prohibition, which had been enacted nationwide with the 18th Amendment in 1920. Under this amendment, the manufacture, sale, and transportation of alcohol were banned in the United States, leading to a complex underground economy around illicit alcohol. In this context, some individuals began to exploit loopholes in the law, obtaining prescriptions for beer and liquor under the guise of medical necessity. Doctors were often persuaded to prescribe alcohol for various ailments, which raised concerns over the integrity of the medical profession and the effectiveness of Prohibition laws.

Under the leadership of President Warren G. Harding, the Willis–Campbell Act was enacted to eliminate the practice, specifically prohibiting the prescribing of alcoholic beverages for medicinal purposes. This law symbolized an effort by the federal government to impose stricter regulations and emphasize the seriousness of adhering to Prohibition. While it did not outright end the consumption of alcohol during this period, it represented a shift toward more stringent enforcement and served as a reflection of the tensions between enforcement and personal liberties.

The signing of the act also sparked debates about individual rights versus government control, raising questions about where the line should be drawn in regulating substances for health purposes. This legislation was part of a broader narrative of the 1920s, characterized by a culture that increasingly associated alcohol with social problems, criminal activity, and moral decay. Over time, the consequences of Prohibition, including the rise of organized crime, led to the eventual repeal of the 18th Amendment in 1933, marking a significant turn in American social and legal landscapes.