It has a southern terminus at the Colorado border south of Sidney and a northern terminus west of Sidney at an intersection with U.S. Highway 30.

Nebraska Highway 19 begins at the Colorado border at a point which is also the north terminus of Colorado State Highway 113.

It continues due north and ends at U.S. Highway 30 west of Sidney.

It followed the original route of U.S. Highway 385, going north to the South Dakota border.

In 1958, US 385 was designated over the former route of Nebraska Highway 19 north of Sidney.