The valley is most distinct in central Chester County, although traces of it can be followed almost the entire distance between the Delaware and Susquehanna rivers.
Multiple branches of both the Brandywine and Octoraro creeks cross the valley.
Significant communities in the Great Valley include, from east to west, King of Prussia, Valley Forge, Chesterbrook, Paoli, Malvern, Exton, Downingtown, Thorndale, Coatesville, Parkesburg, and Atglen.
The Great Valley forms a natural route to the west from the Philadelphia area.
Both the Pennsylvania Turnpike and U.S. Route 202 follow the eastern portion of the valley.