Murchison Falls National Park History bases on the great explorers John Speke and James Grant, these were the first Europeans to visit the present day Murchison Falls National Park in 1862. It was more thoroughly explored by Samuel and Florence Baker in 1863-4. Baker was exited about the nature of the falls, thus named the falls Murchison Falls after the geologist Roderick Murchison, then the president of the Royal Geographical Society.

Between 1907 and 1912, the inhabitants of an area of about 13,000 square kilometres (5,000 sq mi) were evacuated due to sleeping sickness spread by tse-tse flies. In 1910, the Bunyoro Game Reserve was created south of the River Nile. That area roughly corresponds to the part of the MFNP that is in the districts of Buliisa, Masindi, and Kiryandongo. In 1928, the boundaries were extended north of the river into the modern-day Nwoya District.

In 1952, the British administration established the National Parks Act of Uganda. The area described above became Murchison Falls National Park.