The residents, helped by firefighters, volunteers and state troopers, passed submerged cars as they departed on school buses from the Peach Tree Village assisted living facility in Brandon, about a 12-mile drive east of downtown Jackson.
Rain piling up quickly led to some flash flooding in southern Mississippi and Alabama, according to CNN meteorologist Brandon Miller.
"Once the current round of storms taper off tonight, the threat really lessens," Miller added. While some showers and afternoon thunderstorms remain in the forecast for the next several days, the coverage and intensity compared to the past several days are significantly lower.
Nearly 3 feet of water from a nearby creek rushed into the senior living home, forcing the scramble to get its residents to higher ground, according to Brandon Mayor Butch Lee.
Rankin County Constable Gary Windham had "seen water rise in this area before, but not like that," he told WAPT.
About 17 miles away, more than 100 children and 15 employees had to be rescued from the Railroad Center Day Care in Florence due to the fast-rising waters, according to the Rankin County Sheriff's Office.
The children, some carried by local police and day care staff, were evacuated into a school bus and high water rescue vehicles that maneuvered through the flood.
Jackson received more than 8.5 inches from Tuesday to Wednesday, and some areas of Mississippi received more.
Jackson saw 5.05 inches on Wednesday alone, making it the rainiest day in August on record for the city. And Jackson has set a record for the rainiest August on record with seven days still remaining in the month -- 11.57 inches, breaking the previous mark of 11.51 inches set in 2008.
While rainfall isn't expected to be as heavy or widespread Thursday as the last couple of days, more than 5.5 million people still were under flood watches Thursday morning from eastern Texas to Alabama -- including Jackson and Mississippi's southern half, the weather service said.
Some locations in that area could see 2-4 inches, and with the ground already saturated, more flooding is possible.
Roads buckle, train derails under heavy rains
The flooding caused widespread street closures and damaged roads throughout the region.
In Newton County, Highway 489 buckled, creating a gaping hole into which a truck appeared to have fallen.
The weather service had been warning residents not to drive on flooded roadways, saying that even a foot of water could wash away a small vehicle.
As heavy rains pounded the region, the ground gave way under some tracks in Brandon and two pressurized train cars carrying carbon dioxide detached from a train and rolled into a 20-foot ditch, the mayor said.
Brandon officials said the derailment wasn't a hazard to nearby neighborhoods.
There also were multiple reports of water rushing into homes and businesses.
"I haven't seen nothing like this and I've been here for 21 years," another Carthage resident, Abraham Evans, told the station.
Correction: An earlier version of this story misspelled the first name of John Bilbro, an administrator at Peach Tree Village, and the name of the assisted living facility.
CNN's Caitlin Kaiser, Amanda Musa, Dave Hennen and Jamiel Lynch contributed to this report.