With the fall of the Portuguese regime in Angola, South African Airways lost its landing rights in Luanda. In addition to restrictions to overflying African states, there was concern that the country would lose its landing rights at the Ivory Coast and Ilha do Sal, Cape Verde.

Upington Airport's runway was built to accommodate a Boeing 747 with a full load of passengers, cargo and fuel, so that it could take off for Europe without having to stop along the way. Upington was chosen because of its strategic position, availability of land and comparatively lower height above sea level than Johannesburg.

Upington Airport was opened in 1968 as Pierre van Ryneveld Airport. In 1974, a corrugated iron fire station was erected but this structure was converted into administrative offices for airport management and other administrative staff in 1996 and the fire station was relocated.

From August 1976 to December 1982, South African Airways made use of Upington as a refuelling station for two weekly scheduled Boeing 747 flights to London and Zürich.

The Concorde did flight testing at Upington Airport in June 1976.

As of 2006, Upington Airport was to be developed into a major cargo hub that will serve sub-Saharan Africa directly from South Africa's Northern Cape Province.

As of 2009, planning was also under way at Upington Airport to construct a facility for the long-term parking of mothballed (decommissioned) aircraft.

As well as improvements to the airport itself, ACSA has built a solar farm located on 0.66 hectares of land within the airport precinct, capable of producing 500 kW during peak production each year.