The Knoxville Wildlife Area, located northeast of Lake Berryessa, encompasses approximately 21,500 acres of rugged isolated land. Berryessa Knoxville Road connects Lake Berryessa with Lake County and runs through the wildlife area, crossing Eticera Creek numerous times. It can be impassible during high water. Elevation changes range from 1,000 feet to 2,200 and the area is characterized by serpentine soils. Serpentine soils are high in toxic metals and low in plant nutrients, so the flora is unique and unusual. Songbirds; mammals such as black bear, mountain lion and bobcats; amphibians; and reptiles including rattlesnakes can be found throughout the Wildlife Area. Native fish species, such as California roach and the Sacramento pike minnow, are plentiful in creeks and streams. During the spring, the wildflowers are amazing.

Hunting of common game species — including deer, wild turkey, quail, rabbit, gray squirrel, dove, pigeon, and bear — is allowed with a Type C Wildlife Area license, and primitive camping is allowed 1/2 a mile off Berryessa Knoxville Road. Some land was used for cattle grazing and many trails (unmarked) run straight off the Road into the hills to the east and west of the road.