The district is one of the most remote places in Vietnam. An Phu was a part of the Tam Phong Long region that had links with Former Phu Nam and was occupied with the Nguyễn Lords in 1757. However today there is little evidence within the district to trace this ancient link.
Thanks to favorable conditions for agricultural cultivation and transport by water the Vietnamese settled in the district area. Chinese traders came along the Mekong and Hau River from Chaozhou and Guangdong and elsewhere along the route to Phnom Penh. The region was an important route in the trade, business strategy, and also strategically. Nguyễn Ánh came through here during the visit Tây Sơn military offensive. In May 1833 during the war, the soldiers across the river in the district. After that time the military battle in 1874 also saw soldiers traverse the Hau River in the area.
During the period against the French and the Vietnam War the area was too remote from other places in Vietnam to constitute and military activity.
In the Daniel Marvin's book Expendable Elite – One Soldier's Journey Into Covert Warfare, he talked about the time he worked there in the Special Forces in 1965-1966. Their camp Dan Nam camped in An Phu and they organized a group of militant Hao Hao forces to support them. He said: "An Phu is the safest place all Vietnam".
There was military invasion from 1977-1978 by Pol Pot and the Khmer Rouge army and almost all of the people in An Phu had to be evacuated (mainly to the Cho Moi, Phu Tan district). The resultant damage was non-significant
