U.S. Route 19 is a north–south U.S. Highway. Despite encroaching Interstate Highways, the route has remained a long-haul route, connecting the Gulf of Mexico with Lake Erie.

The highway's southern terminus is at Memphis, Florida, just north of Bradenton at an intersection with U.S. Route 41. Its northern terminus is in Erie, Pennsylvania, at an intersection with U.S. Route 20 about two miles (3 km) from the shores of Lake Erie.

The length of the highway is 1,377 miles (2,216 km) following the U.S. Route 19E path through North Carolina and Tennessee.There is also a U.S. Route 19W branch that follows an alternate route for 63 miles (101 km) through North Carolina and Tennessee before rejoining with U.S. Route 19E.