Groote Schuur means "Great Barn" in Dutch, and the name reaches back to 1657, when the Dutch East India Company owned the estate and used it as a granary to store grain for the Cape settlement. The property passed through private hands over the following two centuries, eventually belonging to Abraham De Smidt, the Surveyor General of the Cape Colony, before being purchased by Hester Anna van der Byl. The Cape Dutch building sits in Rondebosch on the lower slopes of Devil's Peak, the eastern shoulder of Table Mountain. Its origin as a functional agricultural building gave it a solidity that survived centuries of changing ownership and purpose, though the original structure would barely recognize what it became.

Cecil Rhodes leased Groote Schuur in 1891 and bought it outright in 1893 for sixty thousand pounds. He commissioned the architect Herbert Baker to transform the farm into a residence befitting the diamond magnate and politician who would become Prime Minister of the Cape Colony. A fire in 1896 destroyed much of the original house, giving Baker a nearly blank canvas. He replaced the traditional thatched roof with Welsh slates, added a long stoep overlooking Devil's Peak, built a new wing with a billiard room and a grand hall dominated by a massive fireplace, and hung four Flemish seventeenth-century tapestries depicting America, Africa, Europe, and Victory. Rhodes detested machine-made hardware - every hinge and fitting was replaced with hand-cast brass and bronze. He filled the rooms with traditional Cape furniture, beginning a collection of colonial furnishings that reflected his complicated relationship with the land he had claimed.

On the estate grounds stood a house called The Woolsack, which Rhodes used as a guest house for notable visitors. Its most famous resident was Rudyard Kipling, who spent his winter holidays at The Woolsack between 1898 and 1908. By then known as the Poet of the Empire, Kipling became a friend of Rhodes during these visits and wrote poetry and newspaper articles supporting the British cause in the Boer War and the formation of the Union of South Africa. The Woolsack was transferred to the University of Cape Town in 1980 and now serves as student accommodation - an ironic afterlife for a house that once hosted the man whose poetry celebrated the very imperialism that the university's students would later protest.

From 1910 to 1984, Groote Schuur served as the official Cape Town residence of South African prime ministers. P. W. Botha and F. W. De Klerk continued to use it as a presidential residence, though Botha preferred the nearby Westbrooke estate. The building witnessed decades of political power exercised in the name of apartheid. Then came 4 May 1990. Three months after Mandela's release from prison, he and De Klerk sat down at Groote Schuur to negotiate the terms of South Africa's transition to democracy. The resulting Groote Schuur Minute established a working party to address the release of political prisoners, the granting of temporary immunity to ANC members, and the definition of political offenses. Under Mandela's presidency, the official Cape Town residence shifted to Genadendal. Groote Schuur became a museum, open by appointment only, its rooms holding the ghosts of every era of South African governance from colony to apartheid to democracy.