Nixon declared a state of emergency Monday, and on Tuesday he activated the National Guard to assist first responders and to secure areas evacuated because of the winter storms.
Several roads were blocked into the tourist mecca of Branson, where nearly 200 families were asked to evacuate voluntarily and the Red Cross opened a shelter on the Branson Strip.
At Rockaway Beach near Branson, residents said the flooding, which peaked Monday night, was the worst they'd ever seen.
"I'm usually pretty good about coming up with a game plan, and yesterday, literally my mind shut down, because I didn't know what to do," Rick Pickren, owner of White River Trading Co., an antique store, told NBC station KYTV of Springfield on Tuesday.
Mayor Don Smith, who went door to door with other volunteers to evacuate residents, said the tourist town of 800 "has just been demolished."
"It's devastating, and we are all so exhausted," Smith told the station.
Meanwhile, in Chester, Illinois, just over the state line from Perry County, Missouri, Menard Correctional Center began transferring prisoners to other facilities because of flooding behind the walls in lower-level cell houses and basements.
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Authorities didn't say how many of the prison's 3,700 inmates were forced to move. Five people have been confirmed to have been killed statewide in Illinois.
The Mississippi River spilled over a levee in the Missouri town of West Alton, prompting the mayor to urge everyone in the town of 520 people to evacuate. Interstate 44 was closed near the central Missouri town of Rolla, and a section of Interstate 70 was shut down in southern Illinois.
In some parts of the MIssouri, rivers are expected to crest as high as they did during devastating flooding in 1993, which is known as the "great flood," Nixon said.
The National Weather Service predicted that the Mississippi River at Chester, Illinois, would crest at 49.7 feet Friday, matching the 1993 record, the governor's office said. The Mississippi at Thebes was expected to crest Saturday at a record-breaking 47.5 feet.