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The national park is located in western Uganda, spanning the districts of Kasese, Kamwenge, Bushenyi and Rukungiri. Its location is approximately 376 kilometres (234 mi), by road, southwest of Kampala, Uganda's capital and largest city. The town of Kasese lies just outside the northeastern edge of the park, while the town of Bushenyi, is situated just outside the park's southeastern boundaries. The coordinates of the park are: 00 12S, 30 00E (Latitude:0.2000; Longitude:30.0000).

Queen Elizabeth National Park occupies an estimated 1,978 square kilometres (764 sq mi), of which, about 17% lies in Kasese District, 50% in Bushenyi District and an estimated 33% lies in Rukungiri District. The area of the park extends from Lake George in the northeast to Lake Edward in the southwest, and includes the Kazinga Channel that connects the two lakes.

The park is named after Queen Elizabeth II and was established in 1954. QENP is known for its wildlife, although many animals were killed in the Uganda-Tanzania War. Many species have recovered, including hippopotamuses, elephants, leopards, lions and chimpanzees; it is now home to 95 species of mammal and 606 species of birds. Owing to the park's biodiversity, it is very suitable for wildlife lovers interested in Uganda tours as one of the major tourist destinations in East Africa.

Elsewhere, the remote Ishasha Sector is famed for its tree-climbing lions, the Kyambura Gorge harbours habituated chimps, the Maramagambo Forest is home to an alluring selection of forest monkeys and birds, and flocks of flamingos are resident on the crater lakes.

The park is also famous for its volcanic features, comprising volcanic cones and deep craters, many with crater lakes such as Lake Katwe, from which salt is extracted.

The national park includes the Maramagambo Forest and borders Kigezi Game Reserve, Kyambura Game Reserve and Kibale National Park in Uganda, and the  Virunga National Park in the Democratic Republic of Congo.