US 340 meets the eastern end of SR 254 (Poplar Avenue) and passes by Waynesboro High School, the Fishburne Military School, and the historic Plumb House and Coiner-Quesenbery House in the Waynesboro Downtown Historic District. The U.S. Highway crosses the South River and intersects US 250 at the east end of Broad Street. The two highways run concurrently east along four-lane Main Street and under Norfolk Southern Railway's Roanoke District to Delphine Avenue, onto which US 340 turns north. The five-lane street with center turn lane passes through the Basic City portion of Waynesboro, where the highway passes under the Buckingham Branch Railroad, crosses Steel Run, and passes by Fairfax Hall. US 340 passes the General Electric Specialty Control Plant and parallels the Norfolk Southern rail line north out of the city and back into Augusta County.