Ball pythons are found in western to central Africa, just north of the equator. They are found in grasslands and open forests, and in areas with some cover. They are typically found near open water so they can cool themselves during hot weather. They spend most of their time on or in burrows under the ground, although they are able to climb. They are primarily nocturnal and active during the wet season. Bush fires can also affect ball pythons. In addition, farmers may kill ball pythons out of fear.
Ticks are primary parasites, with a slightly higher tick burden in males than females. This may be due to the prolonged periods of immobility in females during the two months of brooding their clutch. Male movement to capitalize on encounters with females may increase their risk of exposure to ticks. There are also internal parasites found in ball pythons including, Trypanosoma varani, Helpatozoon (Apicomplexa: Adelorina), and Spinicauda regiensis.