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The Madikwe region is richly steeped in history. Famous figures such as David Livingston, Cecil John Rhodes and the Zulu chief Mzilikazi all left their mark in this corner of South Africa.  But traces of humanity in the area stretch far into the distant past. Middle Stone Age artefacts dating back 250 000 years have been found in Madikwe and several Iron Age sites, dating from 1400 to 1700 AD have been discovered.

Artefacts from the Khoisan, or bushman, people have also been found lying in forgotten valleys and caves in the region.

In the early 19th century, a large Tswana village was thriving near the centre of what is now the reserve. During this period, known as the Difaqane, a violent period of unrest in South Africa, civil wars raged across the Madikwe region, almost destroying the Tswana culture in the area. The name Marico is derived from a Tswana word meaning ‘drenched with blood’ – a reference to a battle in 1823 where the Hurutshe town of Kaditshwene in the Marico River valley, one of the largest towns in southern Africa at that time, was completely destroyed.

In 1832 the renegade Zulu chief, Mzilikazi, escaping from the great Zulu chief Shaka, swept through the area, destroying the Tswana settlements in his path. In the mid 1830’s the famous hunter William Cornwallis Harris passed through the area. David Livingston visited the region several times in the 1840s and lived in the area between 1846 and 1847. Another famous hunter, Frederick Courtney Selous, passed through the region several times between 1875 and 1884, while following the Marico River in search of trophy elephants. The area also has a rich missionary history, with a chapel being built in what is now the south of the reserve in 1886.

In 1899, during the second Anglo-Boer war, the battle of Derdepoort was fought very close to where Makanyane Safari Lodge stands today. This region is familiar to many South Africans through the humorous and incisive writings of the well known author, Herman Charles Bosman, who lived in the area in 1926 and who wrote many unforgettable stories revolving around the characters and places in what was to become the Madikwe Game Reserve.