The history of the Mapungubwe Cultural Landscape dates back 210 million years ago when one of the earliest plant-eating dinosaurs, Plateosauravus (Euskelosaurus), was known to have lived in the area.

The Mapungubwe area became a focus of agricultural research in the 1920s through the efforts of the botanist Illtyd Buller Pole-Evans.

At the request of Jan Smuts, the government set aside a block of nine farms in this area as a preserve for wildlife and natural vegetation in 1918.

Pole-Evans lobbied to have the reserve proclaimed as a national park, with the support of Prime Minister Smuts.

In 1944, Minister of Lands Andrew Conroy proposed the formation of the Dongola Wild Life Sanctuary, which would include 124 farms, 86 of which were privately owned.

In one of the longest running debates in the history of the South African parliament, supporters argued that it was necessary to conserve the country's natural assets, that the land set aside for the proposed reserve was unsuitable for agricultural purposes and that the area had a rich archaeology which should be protected.

In 1993, De Beers Consolidated Mines, which had established the Venetia Limpopo Nature Reserve on land that adjoins Greefswald, called for the area to be declared a national park.

In the 21st century, Mapungubwe has been embraced as a site of significance by South Africans and the international community.

It is a dense vegetation community with a closed canopy which occurs in the rich alluvial deposits along the river.

There are also some very large baobabs in the park, with one specimen having a circumference of 31 metres (102 ft).387 bird species have been recorded in Mapungubwe National Park, including Verreaux's eagle, southern pied babbler, crimson-breasted shrike and black-faced waxbill, Meyer's parrot, White-crested helmetshrike, Meves's starling and some flycatcher species, yellow-bellied greenbul, black-backed puffback, range-breasted bushshrike and grey-headed bushshrike, grey-backed camaroptera and Natal spurfowl, western barn owl, African scops owl, Southern white-faced owl, Verreaux's eagle-owl, Pel's fishing owl, pearl-spotted owlet, Kori bustard, chestnut-backed sparrow-larks and wattled starling, Temminck's courser, collared palm thrush and ground hornbill, great white pelican, white-backed night heron, bat hawk, augur buzzard, African hobby, Dickinson's kestrel, green sandpiper, three-banded courser, blue-spotted wood dove, Brown-necked parrot, Senegal coucal, pennant-winged nightjar, blue-cheeked bee-eater, broad-billed roller, racket-tailed roller, African golden oriole and olive-tree warbler.

An open-cast coal mine and power plant are planned in the buffer zone of the national park, which threaten its natural and cultural value.