The route was not straight, but intentionally linked many small towns in the Midwest, Plains and Southwest. With its essentially flat course and favorable weather, the highway became popular as a truck route, thus contributing to the growth of that industry.

After the end of the Second World War, US 66 became the road of choice for returning GIs, and later, their families during vacation season. This sharp rise in tourism in turn gave rise to a burgeoning trade in all manner of roadside attractions from teepee-shaped motels to frozen custard stands; Indian curio shops to reptile farms.