The designation "Southern Rhodesia"  (a reflection of Rhodes' popularity among settlers, who had been using the name informally since 1891) was officially changed in May 1895 from "Zambesia" after the Zambezi River flowing through the middle.

Cecil John Rhodes first arrived in South Africa in 1870. In the early 1870's he staked a claim with his brother in the just opened Kimberley diamond fields. With his return to England he enrolled at Oxford University, but repeated visits to South Africa delayed his graduation until the early 1880's. (It is thought that his 1875 trek through the rich territories of Transvaal and Bechuanaland helped to inspire the dream of British rule over all southern Africa; the "Cape to Cairo"). As his control of the diamond-mining industry developed, he formed the De Beers Mining Company in 1880 (which once marketed 90% of the world's rough diamonds), but Rhodes was already focussing on the north of the Limpopo as administrator of the British South Africa Company. In 1881, Rhodes entered the Parliament of Cape Colony, in which he held a seat for the remainder of his life. Rhodes became the prime minister of Cape Colony in 1890 and implemented laws that would benefit mine and industry owners (he also conspired to overthrow the South African government of Paul Kruger, and a committee of the British House of Commons was later to pronounce him guilty of grave breaches of duty as prime minister). In 1895 Rhodes supported an attack on the Transvaal, the Jameson Raid, which was a complete failure, forcing Rhodes' resignation as Prime Minister of Cape Colony and leading indirectly to the outbreak of both the Second Matabele War and the Second Boer War.

Meanwhile, John Moffat (son of the missionary Robert Moffat, who was trusted by Lobengula - the Matabele king) had persuaded Lobengula to sign the Moffat Treaty, by which the Matabele agreed not to enter into correspondence or treaty with any foreign power without the sanction of the British High Commissioner for South Africa (despite opposition from the governments of the Transvaal and Portugal). More important was the Rudd Concession, which both gained the trust of Lobengula and transferred major commercial and legal powers to Rhodes - apparently Lobengula had been told that no more than ten white men would mine in Matabeleland (although this was left out of the actual document Lobengula signed, and the British government refused to allow Lobengula`s renunciation). To continue his political games, Rhodes ensured that scouts in the Rudd party secretly agitated the Shona, who believed that the emerging problems were being caused by the Matebele. This helped to ensure the 1888 agreement by which Rhodes secured mining concessions in Matebeleland and Mashonaland. His creation of the British South Africa Company soon established his complete control of the territory; his involvement would prevent any expansion northwards by the Boers, or internationally by the Germans or Portuguese, although his attempts for further expansion were failures. The Belgians succeeded in taking over the Congo, despite Rhode's efforts, and Nyasaland (Malawi) remained a British protectorate, largely due to the presence of British missionaries seeking to end the slave trade. 

The first pioneer column of 180 men and 500 troops left Kimberley in May 1890, and established Fort Victoria in August 1890. A party of pioneers, (including Courtney Selous, after whom the Selous Scouts were named), continued further northwards, and in September 1890 established Salisbury. During the Boer war, Rhodes commanded troops at Kimberley.

Following his death, he was buried at the Matopos Hills (in the same grave as both both Leander Starr Jameson and the 34 white soldiers killed in the Shangani Patrol). The Rhodes Scholarships to Oxford remain one of the beneficiaries of his estate.