Ke holo nei ka muliwaiʻo Potomac i 383 mile mai Fairfax Stone, West Virginia a Point Lookout, Maryland. Loaʻa iā ia ma mua o 6 miliona mau kānaka e noho nei i loko o ka waiwai wai o Potomac, ka'āina 14,670-mile mile kahi e holo ai ka wai i ka waha o ka muliwai. Hōʻike kēia palapala'āina i ka wahi o ka muliwai a me kona wahi wai eʻauʻau nei ma'ō aku o nā māhele'āina e pili ana i ka Appalachian Plateau, Ridge & Valley, Blue Ridge, Piedmont, a me Coast Plalain.
ʻO ke poʻo nui a me nā uku nui nui he 12,878.8 mile ka hanaʻana i ka muliwaiʻo Potomac i ka 21st i ka United States. ʻO nā mea koʻikoʻi o ka muliwaiʻo Potomac,ʻo iaʻo Branch Branch,ʻo Savage River, South Branch, Cacapon, Shenandoah, Antietam Creek, River Monocacy, a me ka muliwaiʻo Anacostia. ʻO ka Potomac ua komo i loko o ke kahawaiʻo Chesapeake .