The Mississippi River forms the eastern border of Missouri. In the past the river carried Native Americans, explorers, early settlers and Lewis and Clark. Today this historic river transports agricultural products, provides recreational venues and scenic views, and is home to many historical sites and communities.

The Great River Road, a scenic byway, follows the Mississippi River valley through a variety of landscapes. In the northeast, a flat agricultural plain meets the Mississippi. South of Hannibal, Lincoln Hills, an area of bluffs, springs and rugged hills transitions into the wooded valleys of the Missouri River bottom. From St. Louis south, rolling hills along the edge of the Ozark Mountain region border the river. South of Cape Girardeau the river bottom is a heavily farmed alluvial flood plain.

Many of the cities along the river feature historical sites and buildings and provide visitors with unique lodging, dining, shopping and entertainment options. In St. Louis, the Jefferson National Expansion Memorial and Museum of Westward Expansion have special exhibits commemorating the Lewis and Clark expedition. Hannibal, hometown of the Mark Twain, offers river cruises and Twain-themed entertainment venues. At Sainte Genevieve, the first permanent settlement west of the Mississippi, visitors can tour historic French colonial buildings, shop for antiques and spend the night at one of several bed and breakfasts.

Wildlife areas along northern section of the river provide access for hunting, fishing and bird watching. The Great River National Wildlife Refuge near Canton has trails and observation decks, and allows hunting and fishing. North of Louisiana, the Ted Shanks Wildlife Area offers camping, a boat access and fishing. Lock and dam #24, near Clarksville provides views of bald eagles.

The Mississippi River area is accessible off of Interstate Highway 55 and State Highway 79. National chains, local hotels and motels, and bed and breakfasts are available in the towns and cities along the way.