The 75,000 hectare Madikwe Game Reserve is located in the North West Province of South Africa, some eighty kilometres north of the town of Zeerust. The Dwarsberg range of hills forms the southern boundary of the reserve, while the border of the neighbouring Botswana forms the northern boundary. The Marico River, the only perennial river in the reserve, runs along the eastern boundary and the main Zeerust-Gaborone road forms the western boundary of the reserve

Madikwe consists mainly of gently sloping plains. In the south of the reserve, the predominant soils are black clay soils overlying principally dolomite and chert. In the northern section of the reserve, the black clay soils are also the most common soil, covering chiefly granite rock. In the northwest of the reserve, the plains are dramatically broken by hills, referred to as Inselbergs, consisting mainly of Modipe gabbro, which rise to over 200 meters above the plains.

Two ranges of hills are found in the reserve, the Dwarsberg in the south, consisting largely of quartzite and shale, and the central Rant van Tweedepoort, a low ridge running east-west, roughly bisecting the reserve, which is made up mainly of quartzite. The rant van Tweedepoort culminates in two peaks, known as Tshwene Tshwene, (Tshwene is the Tswana word for the Chucma baboon), which more or less mark the centre of the reserve. The Marico River cuts into the landscape, creating a shallow, verdant valley running north to south along the reserve's eastern boundary.

The vegetation of Madikwe can be divided into two main groups: broad-leaved communities, dominated by various species of bushwillow, and microphyllous (fine leaved) communities dominated by various species of thorn tree. Common trees in the reserve include the fruit bearing Maroela, (Sclerocarya birrea), the distinctive Shepherd tree (Boscia albitruca) the Leadwood (Combretum imberbe) and the Red Bushwillow (Combretum apiculatum). The Silver Cluster-leaf (Terminalia sericea), the Black thorn (Acacia mellifera) and the Umbrella thorn (Acacia tortillas) are also common in the reserve. Various species of raisin bush (Grewia spp) and guarri (Euclea spp) are widely distributed. Common grasses include Blue buffalo grass (cenhcrus ciliaris) and the Turpentine grasses (Cymbopogon spp).