With adults reaching lengths of over 6 m (20 ft), this is one of the worlds largest species of snakes. The typical adult length is 4.8 m (16 ft), but reports of specimens range to as large as the 9.72 m (32.1 ft) giant caught in Bingerville, Ivory Coast in 1932.

The color pattern is typically brown, with olive and tan irregular blotching, fading to white on the underside. At a glance they can be easily mistaken for the Burmese python, P. m. bivittatus, but the two species are not closely related.

Found in Africa south of the Sahara from Senegal east to Ethiopia and Somalia, including Guinea-Bissau, Mali, Guinea, Sierra Leone, Liberia, Ivory Coast, Upper Volta, Ghana, Togo, Niger, Nigeria, Cameroon, Equatorial Guinea, Chad, Central African Republic, Democratic Republic of the Congo, Angola, Rwanda, Burundi, Sudan, Uganda, Kenya, Tanzania, Zambia, Malawi, Mozambique, Zimbabwe south to northern Namibia, Botswana and northeastern South Africa (to Natal). Extirpated from eastern Cape Province in 1927. The type locality given is "America" -- an obvious mistake. According to Loveridge (1936), no type locality was given. According to Stimson (1969) it was "Guiara, Brazil."

They are typically associated with grassland and savannah habitat, not too far from water (rivers, streams, marshes), sometimes entering the edges of forests. They often occur in or near cane fields.

While not considered endangered or threatened, this species is listed as a CITES Appendix II species, which puts restrictions on its exportation around the world. The primary reason for this is because their skin is used in the leather industry, frequently being made into shoes, belts, and purses.

They are highly dependent on sources of water; they estivate during the hottest and dryest parts of the year, remaining deep in burrows made by other animals. They are noted for their bad temperament and readiness to bite if harassed. This is in contrast to the Burmese python, P. molurus, that is typically docile except when food is near.

They are opportunistic feeders, and will consume almost any animal they come across and can overpower by constriction. Young pythons eat primarily small rodents, which makes them popular with local farmers for reducing the populations of species harmful to crops, like the cane rat. However, adults are capable of taking very large prey, including young crocodiles, goats and gazelles, making them a potential danger to livestock.  Attacks on humans are very uncommon. Although this species can easily kill an adult, there are only a few cases in which the victim, in most cases a child, was actually consumed.

Reproduction occurs in the spring with females laying as many as 100 eggs at a time. They guard their eggs aggressively while they incubate for 2-3 months. Hatchlings are between 45-60 cm (18-24 inches) in length and appear virtually identical to adults, except with more contrasting colors.

This species is commonly the subject of captive breeding and is readily available in the exotic pet trade. They adapt well to captivity, feed willingly on commercially available rats and rabbits. However, their duller coloration and poor temperament generally makes them less desirable than other python species, while their large size and voracious appetite makes them suitable only for the most experienced of large snake keepers.  In addition, Florida law now requires a permit and a fee to keep this species as a pet.

One or both females may be seen in the tent area near the entrance to the Africa exhibit.