It was designated a UNESCO World Heritage Site in 1982, owing to its high levels of biodiversity and vast, undisturbed natural landscapes, such as the grasslands and the miombo woodlands habitat.

Among the numerous species within the park are some of the continent's largest and most iconic (and most vulnerable, threatened or endangered), such as the bush elephant, black rhinoceros, hippopotamus, lion, leopard, spotted hyena, painted dog, Cape buffalo, Masai giraffe, plains zebra, white-bearded gnu and the giant Nile crocodile.

Due to the fragility and sensitivity of the many species and ecosystems within the park, human habitation is not permitted within its bounds, and all persons entering and exiting are tallied and tracked by the Wildlife Division of the Tanzanian Ministry of Natural Resources and Tourism.

[10] Interesting sites in the park include the Rufiji River, which flows into the Indian Ocean opposite Mafia Island, and Stiegler Gorge, a canyon measuring nearly 100 metres deep by as wide.

Although total wildlife populations are high,[11] the reserve is vast; densities of observable animals may be lower than in the busier parks in Tanzania's northern tourist circuit (such as the Serengeti).