The tornado touched down near the intersection of Highway 81 and Interstate 40, according to Fox News. At least two people were killed and several reported missing, according to local emergency services.
A mobile home park in the area was almost totally deestroyed.
El Reno City Councilwoman Tracey Rider said that there had been an unknown number of fatalities at the American Budget Value Inn, which was hit by the tornado, according to News 9, a CBS TV media outlet.
In turn, El Reno Mayor Matt White did not confirm or deny any fatalities.
"It's been a serious, serious event here," he said. "We have all hands on deck."
Highway 81 is closed near the area due to debris and downed power lines, according to the Oklahoma Department of Transportation.
Earlier, the US National Weather Service (NWS) issued a tornado watch for sections of Oklahoma and Texas following a weekend of storms in Nebraska and Texas.