It traveled along the west side of the city in a northwesterly direction, through rolling farmlands and near coal mines, for 72.3 miles (116.4 km) before meeting its northern terminus at an interchange with US 60 in Owensboro.

In 1973, the Glen Lily Road (KY 2665) overpass over the parkway was awarded the title of "Most Beautiful Bridge" by the American Institute of Steel Construction in the Highway Grade Separation category.

However, the newly designed marker signs that were installed on the Natcher Parkway in mid-2006 did not bear the words "Green River".

[10] In November 2011, the Natcher was extended by an additional 2.1 miles (3.4 km) from I-65 southward to US 231 (Scottsville Road) on the south side of Bowling Green.

The East–West Trans America Highway was proposed in the Intermodal Surface Transportation Efficiency Act of 1991 and was narrowed down to the I-66 Southern Kentucky Corridor in the National Highway System Designation Act of 1995:In 1995, the National Highway System Designation Act amended Section 1105 (c) (3) of ISTEA and in Kentucky listed I-66 as centered on the cities of Pikeville, Jenkins, Hazard, London, Somerset, Columbia, Bowling Green, Hopkinsville, Benton and Paducah.

The Southern Kentucky Corridor (I-66) would connect with the proposed King Coal Highway (also called I-73 / 74 North-South Corridor) in West Virginia as listed in Section 1105 (c) (5) in ISTEA (1991).The preferred I-66 route followed US 68 between Bowling Green and Hopkinsville, however the I-66 spur along the Natcher Parkway eventually entered the highway plans.

The William H. Natcher Parkway designation was decommissioned in favor of a new Interstate Highway number along most of its length.

Traffic flow was restricted to one lane, wide loads were prohibited, and the speed limit set to 55 miles per hour (89 km/h).

A new interchange will likely be constructed between the mile markers 3.4 and 4, allowing access to Elrod Road in Bowling Green.