The 300 Area is a small industrialized zone of approximately 0.52 square miles (1.35 square km) located about 1 mile (1.6 km) north of the Richland city limits. It had two main functions: fabricating uranium reactor fuel and research aimed at improving the production process.

During the Cold War, many of the laboratories researched ways to expand and improve weapons production. Although some research and development on radioactive materials still takes place in the 300 Area, most of the old laboratories are being deactivated. Buildings have either already been or are currently being deactivated. Most of the buildings are planned to be demolished eventually.

As of September of 2007, approximately 132 of the 220 total facilities have been demolished. Liquid and solid wastes from operations in the 300 Area were disposed in unlined liquid landfills and burial grounds outside the main complex. Two large burial grounds that received waste from the 300 Area are located several miles from the core industrial area and contain low- to high-activity waste and transuranic contaminated waste. Several buildings in the 300 Area are part of the Pacific Northwest National Laboratory. Over 760,000 metric tons (840,000 tons) of soil and debris have been removed from the 300 Area and disposed of at ERDF.