The Mabuasehube Game Reserve is located in the Kalahari Desert covering an area of almost 2,000 sq. km. The unforgiving desert terrain is characterised by high red dunes and scattered vegetation. In 1992 the reserve was incorporated into the Gemsbok National Park, and in 2000 it was also integrated into the Kgalagadi Transfrontier Park.

The reserve's name is derived from the Senalonga language, and means "red earth". The reserve was once home to the San people, sometimes called Bushman, and to small groups of inhabitants called Kgalagadi.

Mabuasehube Game Reserve offers camping facilities at each of the salty clay pans at Lesholoago, Mabuasehube, Monamodi, Bosobogolo, Mpayathutlwa (sometimes spelled Mpaathutlwa), Khiding and Malatso. Before camping in the reserve, visitors must first obtain a permit. Only one party of visitors is allowed at the campsites at a time, ensuring privacy. The rustic campsites are unfenced and do not have electricity or running water. Therefore visitors are required to bring adequate supplies of fuel, food and water. Access to the reserve is best achieved with 4x4 vehicles, as the roads are sandy and often difficult to navigate.

Those who visit the reserve will discover a dramatic and contrasted landscape.. The main attractions at Mabuasehube are the three large salt pans and various smaller ones, which are all divided by small sand dunes. Due to the  harsh climate of the region large herds of game of gemsbok and eland are attracted to these pans for both water and to lick salt.

Other species of wildlife regularly sighted at Mabuasehube include lion, leopard, wild dog, cheetah, both brown and spotted hyena, warthog, bat-eared foxes, jackal, springbok, wildebeest, oryx, kudu, steenbok, duiker, and a variety of other antelope.

The reserve is also home to an interesting bird list, which totals more 170 species, including Kori bastard, secretary bird, eagle, vulture and buzzard. A variety of water fowl also make their way to the region after heavy rains.