Water levels are still rising along the Ohio and Mississippi Rivers and forecasters warn that even more substantial rain is coming next week.
Tens of thousands of people across the region are expected to evacuate. The flooding is already breaking high-water records that have stood since the 1930s.
"We're getting our mamma and daddy out," Ken Gelston told the Associated Press, who helped pack furniture, photos, and other belongings into pickup trucks in Greenville, Miss.
His parents' house sits on Eagle Lake, which the Army Corps of Engineers expects to rise significantly.
"We could have 5 feet of water in there," Gelston said, nodding at the house. "That's what they're telling us."
Parts of the Mississippi Delta are also beginning to flood. Emergency officials warned that residents may need to leave their homes as the river rises toward an expected crest Wednesday of 48 feet - about 3 feet higher than Thursday. The record in Memphis, 48.7 feet, was set in 1937.
The pressure on the Mississippi and surrounding river levees is so bad that the federal government has actually conducted a series of explosions to reduce the high waters.
One blast at a southeast Missouri levee saved several populated towns, although it flooded more than 100,000 acres of farmland.
Vermont and upstate New York are also coping with floodwaters. Lake Champlain is overflowing and flooding the surrounding countryside, creeping into homes, businesses, and neighborhoods.