It was first established as an airline in March 1969 by Safmarine and started operations on 18 March 1970. Its primary client in the 1980s was the South African Defence Force. Until the 1990s it mainly served the local and regional air cargo market. In 1991 it diversified into aircraft maintenance and overnight courier operations before concentrating on leasing and chartering. In 1998 it purchased a 49% stake in Air Contractors, based in Ireland, and was itself acquired by Imperial Holdings for $40 million in December 1998. In July 1999 Safair acquired control of National Airways Corporation and Streamline Aviation (a charter and aircraft sales company). It is wholly owned by ASL Aviation Group Ltd based in Dublin, Ireland, a subsidiary of the Belgian group Compagnie Maritime Belge. Humanitarian Aid and Relief operations has always been Safair's "niche" market. Safair assists aid and relief agencies such as the United Nations, World Food Programme and the International Committee of the Red Cross in delivering much needed humanitarian aid to stricken regions on the African continent as well as other areas in the world where such assistance is required. In 2007, Safair obtained its IATA Operational Safety Audit (IOSA) approval.
In 2013, Safair created a low-cost carrier subsidiary called FlySafair. The initial plan to operate flights in October 2013 had to be cancelled, as a result of a high-court application by Comair. FlySafair is currently operational with the first flight having taken place on 16 October 2014. FlySafair operates to Cape Town, George, Port Elizabeth and Johannesburg, with plans to serve Durban and East London.