Ghana Airways was founded on 4 July 1958 by the government of Ghana with start up capital of ₤400,000; the government holding a 60 percent stake, with BOAC holding the remainder. When the company was founded, a seven-year agreement between the airline and BOAC was signed, which saw BOAC personnel being seconded to Accra, and Ghanaian personnel being trained in order for them to take over management and operation of the airline. Prior to the foundation of the company, BOAC and West African Airways Corporation were responsible for international services from Ghana, operating pool services from West Africa to London. For their initial operations, Ghana Airways joined the pool services, when BOAC began operating the Accra–London route on 16 July 1958 with a , with the aircraft being operated with the Ghanaian flag and in a livery minimally adapted from that of the UK carrier. The airline's relationship with West African Airways ceased on 30 September, and on 1 October they began operating the domestic and regional flights formerly offered by WAAC . The airline's first aircraft, and hence the first aircraft to be registered in Ghana since the nation became independent, was a de Havilland Heron delivered on 30 December. At the end of the airline's first year of operation they had made a net profit of US$28,000.

A second Heron was delivered to the airline in 1959, and on 9 March the first Douglas DC-3 entered service. Flights to London employed Bristol Britannia 102s wet-leased from BOAC from 16 April, leading to a reduction in Stratocruiser services and the retirement of the type after its final departure for London, via Barcelona, on 31 August. (BOAC's own Stratocruiser services on the route had ceased on 31 May.) By the end of 1959, an order for two Britannias was placed and a service to Conakry was introduced. In 1960 three Vickers Viscounts were ordered on 20 April. Ghanaian President Kwame Nkrumah was accused of being too aligned to the West, and hence he entered into agreements with the Soviets and on 18 August six Ilyushin Il-18s, at a cost of ₤670,000 each, were ordered. After having initially expected to be delivered on 20 November, the first two of six Il-18s was delivered to Accra on 3 December, and were initially crewed and maintained by Soviet personnel while Ghanaian personnel were trained. The aircraft entered service on routes from Accra to Lagos and Dakar, to Addis Ababa via Kano, and Nairobi via Léopoldville. Net profits for the year 1960 totalled US$462,000. In November 1960, the USSR also delivered a single Antonov An-12 to Ghana Airways.

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