The scheme saw off competition from the Canadian War Museum in Ottawa, by Moriyama and Teshima, and the Terrence Donnelly Centre in Toronto, by Behnisch Architekten with Architects Allliance, to pick up the award, which aims to recognise outstanding work by a RIBA member outside the EU.
The shortlist for the prize, which is supported by the AJ's sister magazine, the AR, comes from the RIBA International Award winners.
The jury was made up of AR editor Paul Finch, RIBA president Jack Pringle and the institute's Awards Group chair Jeremy Till.
The jury's report said of the building, in New Brighton Port Elizabeth: 'This is the most evocative of locations and symbology for a museum of apartheid and its struggles.
'It is situated in the oldest township in Port Elizabeth where the first act of defiance occurred, when non-white railway workers refused to show their 'passes' to enter railway property.
'To build a museum of the apartheid era in the midst of the township that acted as a crucible for the struggle is an extraordinary achievement.
'The Red Location Museum brilliantly rises to the challenge, using architectural skill of the highest order to produce an unforgettable experience that is both viscerally and intellectually moving.'