The Great Plague (1664–1666) was the last major epidemic of the bubonic plague to occur in the Kingdom of England (modern day United Kingdom). It happened within the centuries-long time period of the Second Pandemic, an extended period of intermittent bubonic plague epidemics which began in Europe in 1347, the first year of the "Black Death" and lasted until 1750.

The Great Plague killed an estimated 100,000 people, about 20% of London's population. Bubonic plague is a disease caused by the Yersinia pestis bacterium which is usually transmitted through the bite of an infected flea, the prime vector for Y. pestis.

The 1654–1666 epidemic was on a far smaller scale than the earlier "Black Death" pandemic; it was remembered afterwards as the "great" plague only because it was the last widespread outbreak of bubonic plague in England during the four-hundred-year timespan of the Second Pandemic.