The San Francisco plague of 1900–1904 was an epidemic of bubonic plague centered on San Francisco's Chinatown. It was the first plague epidemic in the continental United States. The epidemic was recognized by medical authorities in March 1900, but its existence was denied for more than two years by California's Governor Henry Gage. His denial was based on business reasons, to protect the reputations of San Francisco and California and to prevent the loss of revenue due to quarantine. The failure to act quickly may have allowed the disease to establish itself among local animal populations. Federal authorities worked to prove that there was a major health problem, and they isolated the affected area; this undermined Gage's credibility, and he lost the governorship in the 1902 elections. The new governor, George Pardee, implemented public-health measures and the epidemic was stopped in 1904. There were 121 cases identified, resulting in 119 deaths.

San Francisco, officially the City and County of San Francisco, is a commercial, financial, and cultural center in Northern California. With a population of 808,437 residents as of 2022, San Francisco is the fourth most populous city in the U.S. state of California. The city covers a land area of 46.9 square miles at the end of the San Francisco Peninsula, making it the second-most densely populated large U.S. city after New York City and the fifth-most densely populated U.S. county, behind only four New York City boroughs. Among the 92 U.S. cities proper with over 250,000 residents, San Francisco is ranked first by per capita income and sixth by aggregate income as of 2022.