J. Clark Salyer National Wildlife Refuge is located along the Souris River in Bottineau and McHenry Counties in north-central North Dakota. The refuge of extends from the Manitoba border southward for approximately in an area which was once Glacial Lake Souris. The area is old lake bottom and has extremely flat topography and a high density of temporary wetlands.
The Souris River originates in southern Saskatchewan, flows southwest to Velva, North Dakota, and then generally north to join the Assiniboine River in southern Manitoba. The United States portion of the river is long and has a drainage basin of ; of river and of the basin are in Canada. Approximately of the Souris River are within the boundaries of the Refuge.
The area was designated as the Lower Souris National Wildlife Refuge in 1935. It was renamed to be the J. Clark Salyer National Wildlife Refuge in 1967 in honor of John Clark Salyer II, who was chief during 1934 to 1961 of the U.S. Fish and Wildlife Service's Division of Wildlife Refuges.