Named after the Yazoo tribe, it was established to provide waterfowl and other migratory birds in the Mississippi Flyway with nesting, feeding, brooding, and resting habitat.

The refuge office also administers 12,800 acres (51.8 km2) of Farmers Home Administration (FmHA) transfer properties: 42 fee title tracts and 12 easements.

The Service was given permission to purchase additional land in 1960 under the provision of Section 5928 of the Mississippi Code of 1942, re-compiled by Governor Ross R. Barnett.

As land acquisition progressed, habitat management was diversified for mourning doves, wood ducks, Canada geese and colonial wading birds, along with endangered and resident species.

Yazoo National Wildlife Refuge's 12,941 acres (52.4 km2) of undulating Delta soils range from heavy clay to silt loam and limited sand ridges (hot spots).

Refuge staff have utilized this rolling landscape and through the years have installed 96 water control structures creating over 70 impoundments which have provided a myriad of habitats for migratory waterfowl, colonial wading birds, alligators, and other wildlife.

These plantations, some of which are among the oldest on record, now provide unique opportunities for researchers to study the development process for the restoration of bottomland hardwoods over time.

A rotating cycle of management treatments in these 14 ponds provides habitat for waterfowl, shorebirds, long-legged waders, and other water birds.

The boxes are prepared early in the year and checked frequently during nesting season to track hatches and remove non-viable eggs.

During fall, winter and spring, numerous visitors travel refuge roads to observe the diverse wildlife which includes white-tailed deer, wild turkey, waterfowl, bobcat, and otter.

A common resident of the refuge's many sloughs, streams, lakes, and shallow ponds, alligators can often be seen on warm spring days basking on logs or banks, or floating motionless.

Yazoo National Wildlife Refuge offers excellent white-tail deer, squirrel, rabbit, and raccoon hunting opportunities.