It connects the Nebraska state line, south of Vermillion, with the southeastern part of the Madison area, via Viborg, Hurley, Parker, and Humboldt.

SD 19 begins at the Nebraska state line south of Vermillion, in the south-central part of Clay County.

It passes just west of Harold Davidson Field, the airport for Vermillion.

Just south of an intersection with the eastern terminus of Timber Road, the highway curves to the northeast.

Just east of an intersection with the western terminus of West Main Street, they begin the curve to the northeast.

During this curve, they cross over some railroad tracks of BNSF Railway on a road bridge.

Between 312th and 311th streets, it skirts along the eastern edge of Spirit Mound Historic Prairie.

Between an intersection with both the northern terminus of Frog Creek Road and the southern terminus of 459th Avenue and an intersection with 458th Avenue, the highways cross over Klepke Ditch and Frog Creek.

At an intersection with 456th Avenue, SD 19 splits off to the north-northeast and enters Turner County proper.

Between 296th and 295th streets, SD 19 crosses over Frog Creek again and curves to the north-northwest.

They cross over some railroad tracks of BNSF Railway and curve to the north-northwest and enter the city limits of Parker.

At Fourth Street, SD 44 splits off to the west-northwest and heads towards the business district of Parker.

Just south of 274th Street, it crosses over the West Fork Vermillion River.

At an intersection with 268th Street, the highway enters the extreme southwestern part of Minnehaha County.

At this intersection, both highways travel concurrently to the east-southeast, while the roadway continues to the north as 456th Avenue.

Just west of Lake Madison, and just north of 236th Street, the highway curves to the north-northwest.

Just to the west of Bourne Slough, and just south of 235th Street, it begins a curve to the north-northeast.

In November 2001, SD 19's southern terminus was extended southward from Vermilion, when a new bridge to Nebraska was opened.

At this intersection, SD 19A turns left onto State Street and travels to the west-southwest.