Malheur Refuge is located in the southeastern corner of Oregon in a geographic region known as the Northern Great Basin. The refuge is shaped like a lopsided "T" and spans an area 40 miles long and 39 miles wide. Over 187,000 acres of wetlands, riparian areas, meadows, and uplands are managed by the refuge.

Refuge Headquarters is located on the south side of Malheur Lake and is about 32 miles southeast of Burns, Oregon. The refuge and museum are open daily from dawn until dusk. During the summer the Visitors Center at refuge headquarters is open and staffed by volunteers each day from 8:00 am to 4:00 pm.