The Appalachian Regional Commission's unique structure is designed to ensure an active federal-state partnership. There are 14 Commission members: the governors of the 13 Appalachian states and a federal co-chair. The federal co-chair is appointed by the president and is subject to Senate confirmation. Each year the 13 governors elect one of their number to serve as states' co-chair of the Commission.

Each governor appoints an alternate who oversees the state's ARC program and serves as the state-level contact for those seeking ARC assistance. The states' interests at ARC/Washington are handled by the states' Washington representative, who is hired by the states.

Grassroots participation is provided through local development districts, multicounty agencies with boards made up of elected officials, businesspeople, and other local leaders.

The Commission staff is headed by an executive director. The staff comprises about 50 people, most of whom serve as program and financial analysts and researchers. The staff implements the program and policies determined by the federal-state partners. The Commission's administrative costs are shared equally by the federal and state governments. The Commission's office is located in Washington, D.C.; there are no field offices.