The Dorena-Hickman Toll Ferry is one of the few remaining riverboat ferries in the United States and the only operating ferry crossing the Mississippi River between Missouri and Kentucky. A ride on the ferry provides a unique opportunity to experience the wonder and beauty of the Mighty Mississippi.

The Meeting the Ohio River Region is home to two art institutions with rotating exhibits - the Crisp Museum on the campus of Southeast Missouri State University and the Sikeston Depot Museum. The area is also home to a number of farmers markets that are held in the warmer months.

Wickliffe Mounds is the archaeological site of a prehistoric Native American village of the Mississippian mound builders that was occupied from about 1100 AD to 1350 AD. The site features a museum consisting of 3 excavated mounds with archaeological features, Mississippian burial practices, displays of artifacts from the site and a mural of a Mississippian village.

The Fort Jefferson Memorial Cross is a 95-foot memorial that stands high upon a bluff at the confluence of the Ohio and Mississippi Rivers. The site offers a very good view of the confluence of the Mississippi and Ohio Rivers and is also a Lewis and Clark Expedition historic site.

Columbus-Belmont State Park sits on bluffs overlooking the Mississippi River. The park is the site of a Confederate fortification built during the Civil War to prevent Union forces from using the river. There is a 2.5-mile self-guided hiking trail in the Park. The park features seasonal facilities that include a Civil War Museum, a snack bar, gift shop, and miniature golf course.

The Barlow House Museum is a turn-of-the 20th century 11-room Victorian home classic residence. One of the original owner’s sons spent 50 summers traveling the world with the American aristocracy, gradually assembling a unique collection of 20th century artifacts, memorabilia and art. On display in the house are many wonderful examples of Mr. Barlow's varied and valued collections.

Ballard Wildlife Management Area is part of the Mississippi River floodplain and contains approximately 8,200 acres comprised of bottomland hardwoods, interspersed with numerous oxbow lakes, tupelo and cypress swamps, grasslands, and agricultural fields. Most of the area is closed to visitation from October 15 to March 15 annually.

This hand-hewn stone courthouse was completed in 1848 atop a bluff overlooking the Mississippi River. The building was constructed with local sandstone, hewn timbers, hand sawed board, plaster, and with a split shingle roof.  This courthouse was the county seat of Alexander County until 1884 when the county seat was moved to Cairo. Tours may be arranged with advance notice.

Across the street from the Cairo Customs House is the A. B. Safford Memorial Library. This Queen Anne architecture building was constructed in 1883 as a memorial by Mrs. Alfred B. Safford to her husband. Few changes have been made in the red brick building. The library contains a number of cultural items as well as books, maps, and pictures of importance to Cairo and Alexander County history.

Riverlore is a stately white mansion located in the residential section of Cairo once known as "Millionaire's Row" and was the home of Captain William Parker Halliday. The grounds cover 3/4 of an acre and with its exquisitely maintained, landscaped grounds complete with magnolias, flowering trees, shrubs, and is by far the most picturesque mansion in the Cairo community.