Television footage shows flattened buildings and fires after a mile-wide tornado moved through the Oklahoma City area.
Video showed homes and buildings in Moore, Oklahoma, were reduced to rubble, and vehicles littered roadways south and southwest of Oklahoma City.
Several children were pulled out of the rubble alive at a school.
An Associated Press photographer saw several children being pulled out of what was left of the Plaza Towers Elementary School in Moore after the massive tornado hit the region.
Rescue workers lifted children from the rubble before they were passed down a human chain and taken to a triage centre set up in the school's car park.
The suburb of Moore, where the damage was concentrated, was hit hard by a tornado in 1999 that included the highest winds ever recorded near the earth's surface.
The National Weather Service later said the latest tornado had wind speeds up to 200 mph.
The weather service's preliminary classification of Monday afternoon's tornado was an EF-4 on the enhanced Fujita scale.