Lostwood National Wildlife Refuge (NWR) lies in the heart of the Missouri Coteau region, an ancient glacial moraine area. Topography ranges from rolling to steep hills and is covered by mixed-grass prairie. The area is dotted with wetlands that are often called "potholes." At 26,904 acres, the Refuge contains a 5,577-acre Wilderness Area established in 1975. Lostwood NWR has been designated a "Globally Important Bird Area" by the American Bird Conservancy. The Refuge provides breeding habitat for the Great Plains population of the threatened piping plover. Also, many declining grassland-associated bird species, such as Baird's sparrow, benefit from the intensive grassland management programs on the Refuge. Using prescribed burning and grazing, Refuge staff reduce encroachment by exotic plants and woody vegetation. The native mixed-grass community is slowly being restored.

The Lostwood NWR headquarters is located 22 miles north of Stanley, North Dakota, along State Highway 8. Stanley is located 55 miles west of Minot on State Highway 2.