The only known populations are found along the Mpanga River, before its outlet at Lake George, at altitudes between 1,000 and 1,300 m. Encephalartos whitelockii is endemic to a single location, where it forms one of the largest and most impressive cycad populations in Africa in Kamwenga District of the southwestern part of Uganda (possibly the largest single cycads colony in Africa).

Seedlings and small plants are absent from open habitats which may be as a result of too frequent fires, but under forest canopy, prolific regeneration occurs.

Threats to the species includes the construction of a small hydro electric power plant on the Mpanga River Falls, the construction of roads and camps in the cycad belt, causing soil erosion and deep gullies, reducing habitat quality, the reduction in population of mature and young individuals as they are knocked down by heavy machinery and reduction in area of occupancy owing to parts being occupied by weir (reservoir), water canal, and power house.

Moreover, it is reported that the collection of seed and seedlings for commercial trade may impair the regeneration capacity of the cycad and thus lead to further reduction of its population.

Geographically E. whitelockii occurs closest to Encephalartos ituriensis, but these species are separated by the Rift Valley, which probably represents a strong isolating factor.

The survival of the species is seriously threatened by the project for the construction of a hydroelectric power station, approved in 2007, which will lead to the Mpanga River runoff.