If you ever dare to drive the longest road in Missouri, you better be prepared to devote your whole day to it. It's also possibly one of the loneliest roads in America. What is the longest road in Missouri? That's definitely more convenient, but there's also a case to be made that Missouri Route 5 will take you through the old Missouri with some of the small towns that you rarely hear about. If you choose that nostalgic journey, make sure you're careful for oncoming traffic on this sometimes terrifying two-lane road.