The Ports-to-Plains Corridor begins in the south with four-lane Interstate 35 in Laredo, Texas, and then splits off onto two-lane U.S. Route 83 through Carrizo Springs and two-lane U.S. Route 277 through Eagle Pass, Del Rio, Sonora and San Angelo.
In San Angelo it becomes four-lane U.S. Route 87, continuing through Big Spring, Lamesa and up to Lubbock, where it joins with four-lane Interstate 27 and continues north to Amarillo.
Between San Angelo and Big Spring, two-lane U.S. Route 158 splits from the main route and becomes a four-lane highway before it goes through Midland/Odessa. The loop continues up two-lane Texas State Highway 349, rejoining the main route on Texas State Highway 87 in Lamesa.
North of Amarillo, the route becomes four-lane U.S. Route 287/87 to Dumas, where the route splits again. The western leg becomes two-lane Texas State Highway 87 for a time before opening up to four-lanes passing through Dalhart, then continuing as two-lane highway to Clayton, New Mexico. This spur of the route continues through New Mexico as two-lane U.S. Route 64, where it ends at Interstate 25.
The northern route of the corridor continues on four-lane U.S. Route 287 to Stratford and then becomes two-lane as it passes through Boise City, Oklahoma. From there the corridor crosses into Colorado and passes through Springfield, Lamar and Kit Carson, still on U.S. Route 287.
The route continues north on two-lane U.S. Route 40 where it joins four-lane Interstate 70 and terminates in Denver.