At least 116 people died, making it the nation's deadliest single tornado in nearly 60 years and the second major tornado disaster in a month. An unknown number of people were hurt.
Authorities feared the toll could rise as the full scope of the destruction comes into view: House after house reduced to slabs, cars crushed like soda cans, shaken residents roaming streets in search of missing family members. And the danger was by no means over. Fires from gas leaks burned across town, and more violent weather loomed, including the threat of hail, high winds and even more tornadoes.
At daybreak, the city's south side emerged from darkness as a barren, smoky wasteland.
"I've never seen such devastation - just block upon block upon block of homes just completely gone," said former state legislator Gary Burton who showed up to help at a volunteer center at Missouri Southern State University.
It was the nation's deadliest tornado since a June 1953 twister in Flint, Michigan, and authorities were prepared to find more bodies in the rubble throughout Joplin, a gritty, blue-collar town of 50,000 people about 160 miles south of Kansas City.
Despite the grim outlook, Gov. Jay Nixon said he was "optimistic that there are still lives out there to be saved."
While many residents had 10 to 17 minutes of warning, rain and hail may have drowned out the sirens.
Larry Bruffy said he heard the first warning but looked out from his garage and saw nothing. "Five minutes later, the second warning went off," he said. "By the time we tried to get under the house, it already went over us."
As rescuers toiled in the debris, a strong thunderstorm lashed the crippled city. Rescue crews had to move gingerly around downed power lines and jagged chunks of debris as they hunted for victims and hoped for survivors. Fires, gas fumes and unstable buildings posed constant threats.
Teams of searchers fanned out in waves across several square miles. Many of the groups included specially trained dogs. The teams went door to door, making quick checks of property that in many places had been stripped to its foundations or had its walls collapse.
National Weather Service Director Jack Hayes said the storm was given a preliminary label as an EF4 - the second-highest rating given to twisters. The rating is assigned to storms based on the damage they cause. Hayes said the storm had winds of 190 to 198 mph. At times, it was three-quarters of a mile wide.
Some of the most startling damage was at St. John's Regional Medical Center, where staff had only moments to hustle their patients into the hallway. Five patients died there, although it was not clear if they were patients or staff members.
The storm blew out hundreds of windows and caused damage so extensive that doctors had to abandon the hospital after the twister had passed. A crumpled helicopter lay on its side in the parking lot near a single twisted mass of metal that used to be cars.
Dr Jim Roscoe, said some members of his emergency room staff showed up after the tornado with injuries of their own, but they worked through the night anyway.
"I spent most of my life at that hospital," Roscoe said at a triage centre at Joplin's Memorial Hall entertainment venue. "It's awful. I had two pregnant nurses who dove under gurneys ... It's a testimony to the human spirit."
As the tornado bore down on their trailer home, Joshua Wohlford, his pregnant girlfriend and their two toddlers fled to a Walmart store. The family narrowly escaped after a shelf of toys partially collapsed, forming a makeshift tent that shielded them.
"It was 15 minutes of hell," Wohlford said.
At a Fast Trip convenience store, another 20 people ran into a pitch-black cooler as the building began to collapse around them. They documented their experience with a video that was drawing tens of thousands of views online by Monday afternoon. The audio was even more terrifying than the imagery - earsplitting wind, objects getting smashing, wailing children and a woman praying repeatedly.
Brennan Stebbins said the group crouched on the floor, clinging to and comforting each other until they were able to crawl out. No one was seriously hurt.
Shielded by mattresses, former lawmaker Chuck Surface rode out the storm in his basement with his wife, daughter, granddaughter and dog. After about five minutes, the deafening roar abruptly stopped.
"When it got to where we thought we could look out," he said, "we went to the top of the stairs and there was no roof - it was all open air."
Dazed survivors tried to salvage clothes, furniture, family photos and financial records from their flattened or badly damaged homes.
Kelley Fritz rummaged briefly through what was left of a storage building, then gave up. Her boys, both Eagle Scouts, rushed into the neighbourhood after realising every home was destroyed.
When they returned, she said, "my sons had deceased children in their arms."
Others just waited for answers.
Justin Gibson stood outside the tangled remains of a Home Depot and pointed to a black pickup that had been tossed into them. It belonged to his roommate's brother, last seen at the store with his two young daughters.
"I don't know the extent of this yet," Gibson said, "but I know I'll have friends and family dead."
