Saint Paul, the state capital of Minnesota, forms the "Twin Cities" with neighboring Minneapolis. It’s home to the Science Museum of Minnesota, with its dinosaur specimens and immersive theater. The Minnesota History Center has interactive exhibits about the region's history. Nearby is the beaux arts Cathedral of Saint Paul. The Cass Gilbert–designed Minnesota State Capitol features paintings of Civil War scenes.

Red Wing is a city on the Mississippi River in Minnesota. Trails lead up the landmark Barn Bluff, which offers river and city views from its summit. The Pottery Museum of Red Wing traces the history of the local clay industry. The Cannon Valley Trail links Red Wing to the nearby city of Cannon Falls. It travels west through the Welch Village ski resort. To the east, Frontenac State Park is a popular for birdwatching.

La Crosse is a city on the Mississippi River, in western Wisconsin. Riverboats depart from Riverside Park, where the International Friendship Gardens feature landscape styles from around the world. The Riverside Museum traces the city's history. Dahl Auto Museum has restored classic cars. Grandad Bluff Park offers trails and views of the city. The Shrine of Our Lady of Guadalupe is a Catholic site on wooded grounds.

Dubuque is an Iowa city on the Mississippi River. The National Mississippi River Museum and Aquarium explores life in and around the river. Northwest, the Dubuque Arboretum and Botanical Gardens include rose, herb and Japanese gardens. Mathias Ham House is a 19th-century mansion with opulent furnishings, with an 1833 log cabin on its grounds. South, the Mines of Spain State Recreation Area has trails and wildlife.

Burlington is a city in, and the county seat of, Des Moines County, Iowa, United States. The population was 25,663 in the 2010 census, a decline from the 26,839 population in 2000. Burlington is the center of a micropolitan area, which includes West Burlington and Middletown, Iowa, and Gulfport, Illinois

Hannibal is a city on the Mississippi River in northeast Missouri. The Mark Twain Boyhood Home and Museum is where the American writer grew up, and displays artifacts such as his typewriter and writing desk. The Mark Twain Cave Complex served as inspiration for his novels. Completed in 1900, Rockcliffe Mansion features art-nouveau decor and antique furniture. The Mark Twain Riverboat offers trips on the Mississippi. ― Google

St. Louis is a major city in Missouri along the Mississippi River. Its iconic, 630-ft. Gateway Arch, built in the 1960s, honors the early 19th-century explorations of Lewis and Clark and America's westward expansion in general. Replica paddlewheelers ply the river, offering views of the arch. The Soulard district is home to barbecue restaurants and clubs playing blues music.