The park is situated near the foothills of the Rwenzori Mountains and close to the border with the Democratic Republic of Congo.
Its geographical position explains much of its biological significance.
The forest represents an eastern extension of vegetation associated with the Congo Basin, creating habitat for species that are uncommon or absent elsewhere in East Africa.
Travelers usually reach Semuliki by road as part of a western Uganda safari.
The park can be incorporated into a route that also visits Fort Portal, Kibale and Queen Elizabeth National Park.