Population decline can refer to the decline in population of any organism, but this article refers to population decline in humans. It is a term usually used to describe any great reduction in a human population. It can be used to refer to long-term demographic trends, as in urban decay or rural flight, but it is also commonly employed to describe large reductions in population due to violence, disease, or other catastrophes.

Sometimes known as depopulation, population decline is the reduction over time in a region's census. It can be caused for several reasons; notable ones include sub-replacement fertility (along with limited immigration), heavy emigration, disease, famine, and war. History is replete with examples of large scale depopulations. Many wars, for example, have been accompanied by significant depopulations. Prior to the 20th century, population decline was mostly observed due to disease, starvation and/or emigration. The Black Death in Europe, the arrival of Old World diseases to the Americas, the tsetse fly invasion of the Waterberg Massif in South Africa, and the Great Irish Famine have all caused sizable population declines. In modern times, the AIDS epidemic has caused declines in the population of some African countries. Less frequently, population declines are caused by genocide or mass execution; for example, in the 1970s, the population of Cambodia underwent a period of decline due to wide-scale executions by the Khmer Rouge.