 In 1876 he was named acting Delegate of the American Geographical Society to a conference called by King Leopold II of Belgium to organize the International African Association with the purpose of opening up equatorial Africa to civilizing influences.Leopold II used Sanford to convince Henry Morton Stanley to explore the Congo basin for Belgium in 1878.He then hired Sanford in 1883 as his envoy to the United States to try to gain American recognition for his colony in the Congo Basin, which became known as the Congo Free State

In 1886, Sanford organized in Brussels and dispatched to the Congo and its tributaries the Sanford Exploring Expedition for the purpose of scientific and commercial discovery and for the opening up of an interior trade.