It runs 19.62 miles (31.58 km) in a general east–west direction from the main entrance of the Louisiana State Penitentiary at Angola to a junction with U.S. Highway 61 (US 61) north of St. Francisville.

LA 66 winds through the scenic Tunica Hills of West Feliciana Parish and connects the prison facility with US 61, the main highway through the area.

From the west, LA 66 begins at the main entrance to the Louisiana State Penitentiary at Angola, formerly the site of a 19th century plantation now within the boundaries of the prison.

The highway then curves to the northeast, passing between the north and south tracts of the Tunica Hills Wildlife Management Area.

Over the next 4.6 miles (7.4 km), the highway passes through the sparsely populated areas of Turnbull and Weyanoke before intersecting LA 968.

[2] The route is classified as a rural major collector by the Louisiana Department of Transportation and Development (La DOTD).

Its location was formerly the site of several 19th Century plantations on the east bank of the Mississippi River in West Feliciana Parish.

This extension paralleled the Louisiana and Arkansas Railway line which once traversed the property and crossed the Mississippi River by ferry into Pointe Coupee Parish.

[11] It was officially opened as a scenic route in October of that year with a dedication ceremony that included a representative of the Tunica-Biloxi Indian Tribe.

[23] The government of West Feliciana Parish also changed the highway's local name from the generic "Angola Road" to "Tunica Trace" to highlight the route's history.