Near Guymon, the route turns due south to approach the town. US-412 then heads due east, while US-64 veers from due south to northeast, joining up with US-54. These two routes remain together for about , splitting at Hooker, with US-54 continuing northeast into Kansas while US-64 again veers due east. At Turpin, US-64 turns left, running north with US-83; three miles (5 km) later, it again turns east, joining US-270 while US-83 and westbound US-270 continue north to Liberal, Kansas. to the east, US-270 departs to the south, and US-64 finally runs solo for a significant stretch save for very short concurrencies with US-283 near Rosston, US-183 through Buffalo, and US-281 in Alva.