Chowilla Regional Reserve is a type of protected area known as a regional reserve. It is located in South Australia approximately 250 kilometres (160 mi) north-east of Adelaide. It was proclaimed 8 April 1993 in conjunction with the Chowilla Game Reserve and has an area of 75,221 hectares (185,880 acres). ‘It protects and conserves a semi-arid environment adjacent to the Murray River. The dominant land uses of the reserve are pastoral production, conservation of natural and historic features and tourism/recreation.’ 
Chowilla is an Aboriginal name for this district. There were various early spellings by pioneers for the Chowilla Creek anabranch and floodplain. These include Cawilli by Sturt and Kawelle by Browne. Tindale noted Tjowilla, as well as the accepted modern spelling Chowilla. Tindale attributes the meaning to a 'place of spirits or ghosts'.
The Aboriginal inhabitants of the Chowilla region were the Maraura people. The first European exploration was the expedition of Capt Charles Sturt in 1830. There were no further European incursions until 1838, when Hawdon and Bonney were the first to overland livestock between NSW and South Australia. Theirs was the harbinger of numerous such overlanding expeditions over the following years, the increasing pace and scale of which climaxed in conflict known as the Rufus River massacre at nearby Lake Victoria. Hostilities between Aboriginals and Europeans abated following that, such that by 1846 the first pastoralist settlers arrived in the district, led by Fred Handcock, Henry Jones, James Fisher, and Ned Bagot.