U.S. Route 65 is a major north–south United States highway stretching approximately 966 miles from Clayton, Louisiana, to Albert Lea, Minnesota. This route traverses a wide variety of landscapes, linking the Mississippi Delta with the Great Plains and the upper Midwest. Along the way, it passes through key cities and towns such as Little Rock, Arkansas; Springfield, Missouri; and Des Moines, Iowa.

In the southern portion of its route, US 65 winds through the delta farmlands of Louisiana and Arkansas. This stretch is primarily rural and agricultural, marked by small towns, bayous, and wide-open fields. The highway often runs parallel to the Mississippi River and provides a critical link for communities dependent on agriculture and trade. In Little Rock, Arkansas, US 65 briefly merges with Interstate 530, I-30 and I-40, forming part of the region’s major transportation network.

As US 65 continues northward, the landscape shifts to the Ozark Mountains and later to the rolling plains of Missouri and Iowa. The highway provides access to popular tourist areas like Branson, Missouri, a hub for live entertainment and recreation in the Ozarks. Further north, the route enters Iowa, serving as a connector between smaller rural communities and urban centers such as Des Moines. Eventually, it terminates in southern Minnesota at an interchange with I-35, completing its long journey through the heart of the central United States.