During World War II, Takoradi Airport was a major stop on the United States Army Air ForcesAir Transport Command Trans-Africa Ferry Route, as an intermediate stop between Monrovia-Roberts Field, Liberia and Apapa Airport, Nigeria. Takoradi Airport was utilized as a Royal Air Force base where crated aircraft, that had been shipped over the Atlantic, were assembled prior to being flown to operational areas in North Africa. 26 Squadron SAAF was also based in Takoradi during WWII flying Wellington bombers on anti-submarine and convoy protection patrols over the Atlantic. A number of South African Air Force airmen are buried in the Takoradi European Public cemetery adjoining the Airport.
On 24 April 1969, Douglas C-47A 9G-AAF of Ghana Airways crashed on approach to Takoradi Airport, killing one passenger of the 33 passengers and crew. The aircraft was operating a domestic scheduled passenger flight from Kotoka Airport, Accra.