Over the course of time, the Yukon and Kuskokwim rivers created one of the largest river deltas in the world. That delta, a generally flat marshland containing innumerable lakes and ponds, is the dominant landscape of the Yukon Delta Refuge. This region which was once part of the land mass called Beringia, or Bering Land Bridge, has been occupied for thousands of years. It continues to serve as home for over 25,000 people, mostly Yup'ik Eskimos who live in 35 villages scattered throughout the refuge.


Refuge lands were first set aside by President Theodore Roosevelt in 1909 as a preserve and breeding ground for native birds. In 1929, Nunivak Island was set aside as a refuge and breeding ground for wild birds, game, and furbearing animals. In 1930, the small islands and all lands under the waters surrounding Nunivak Island were added to the refuge. Additional lands were reserved by President Franklin D. Roosevelt in 1937 when Hazen Bay Migratory Waterfowl Refuge was established. The Kuskokwim National Wildlife Range, established in 1960, was enlarged in 1961, and its name changed to the Clarence Rhode National Wildlife Range.

On December 2, 1980, President Jimmy Carter signed the Alaska National Interest Lands Conservation Act (ANILCA). With enactment of ANILCA, these existing ranges and refuges were combined and enlarged to establish the Yukon Delta NWR. It was ANILCA that also established the Andreafsky and Nunivak Wilderness Areas and designated the Andreafsky River as a Wild and Scenic River. With the exception of several small additions to the refuge through land exchanges or purchases, all lands that now make up the refuge were in the public domain prior to refuge designation.