US 19 passes through the limits of the cities and towns of Bluefield, Princeton, Beckley, Oak Hill, Fayetteville, Summersville, Flatwoods, Weston, Jane Lew, Clarksburg, Shinnston, Worthington, Monongah, Fairmont, Rivesville, Westover, Morgantown, and Star City, in addition to the smaller communities of Kegley, Spanishburg, Flat Top, Ghent, Cool Ridge, Shady Spring, Daniels, Beaver, Johnstown, Hico, Heaters, Napier, Letch, Ireland, Ben Dale, Homewood, Kitsonville, Hepzibah, Meadowbrook, Enterprise, Arnettsville, and Georgetown.

[2] Between Bluefield and Beckley, US 19 has been largely supplanted by Interstate 77 (I-77) and the West Virginia Turnpike.

Between Prosperity and northeast of Canfield, the route serves as a major southwest–northwest artery as Corridor L of the Appalachian Development Highway System (ADHS).

Aside from the four-lane limited access Corridor L, US 19 remains largely two-lane rural road with numerous curves outside of major cities.

[1] By May 1973, hearings had been planned on widening the highway to four lanes in between Claypool Hill and Lebanon; at that time, such work had been completed between Abingdon and Hansonville, with a contract allocated for work from Hansonville to Lebanon.