Interstate 35 in Moore was closed, Oklahoma Department of Transportation spokesman Cole Hackett said. Crews were heading to the north-south highway to start the cleanup process.
"People are trapped. You are going to see the devastation for days to come," said Betsy Randolph, spokeswoman for Oklahoma Highway Patrol. She did not say how many people were stuck.
More than 38,000 electricity customers in Oklahoma are without power, according to local power providers.
Even as authorities worked to wrap their heads around the damage, NOAA's Bunting warned the worst may be yet to come.
"These storms are going to continue producing additional tornadoes. They'll also produce some very, very large hail, perhaps larger than the size of baseballs. We're also concerned that there may be an enhanced and widespread damaging wind threat with storms as they merge together," he said.
"As bad as today is, this is not over yet."
Oklahoma resident: 'It's just all gone'
The severe weather came after tornadoes and powerful storms ripped through Oklahoma and the Midwest earlier Monday and on Sunday.
Forecasters had said that the destructive weather, which killed at least two people, was perhaps just a preview.
Before Monday afternoon's devastation, residents in areas hard hit by weekend storms were combing through rubble where their homes once stood.
"My mind is, like, blown, completely blown," said Jessie Addington, 21, who found that few pieces of her childhood home in Shawnee, Oklahoma, were still standing Monday.
Addington, who now lives in a nearby town, said her mother huddled in the mobile home's bathroom when the weekend storm hit. But the tornado still tossed her around like a rag doll, leaving her bruised.
When Addington arrived, she was shocked to find the neighborhood where she had lived for 17 years reduced to ruins.
"I'm feeling cheated, to be honest," she said, "like, it's just all gone."
An estimated 300 homes were damaged or destroyed across Oklahoma in weekend weather, Red Cross spokesman Ken Garcia said.
Two men, both in their 70s, were confirmed dead as a result of an earlier tornado that hit Shawnee, said Elliott, the spokeswoman for the state medical examiner's office.
As many as 28 tornadoes were reported in Oklahoma, Kansas, Illinois and Iowa, according to the National Weather Service, with Oklahoma and Kansas the hardest hit. Some of those reports might have been of the same tornado.
A combination of factors -- including strong winds and warm, moist air banging against dry air -- means severe weather could continue sweeping across a wide swath of the United States for days, Petersons said.
"Keep in mind we have all the ingredients out there that we need," she said.
Tornado watches were in effect for portions of southeastern Kansas, western and central Missouri, northwest Arkansas, central and eastern Oklahoma and northwestern Texas until 10 p.m. (11 p.m. ET).