The tornado was one of some 120 twisters reported over the weekend so far in America's Midwest.
Woodward, in the northwest of Oklahoma, was badly damaged in the twister, which struck after midnight, local time.
Reports said two children were among the dead, and one person injured in the storm is believed to be in a critical condition.
The town's mayor, Roscoe Hill, said the tornado hit a mixed area of homes and businesses.
He added it appeared that sirens to warn people of the approaching danger had not worked - even though they had been sounding loudly from storms on Saturday afternoon.
"We had a little tornado earlier... and they blew all the sirens. When this one came in, our sirens weren't working," Mr Hill said.
The National Weather Service (NWS) said there had been some 120 tornado sightings in four US states - Oklahoma, Kansas, Nebraska and Iowa.
Most were recorded in Kansas, where almost 100 twisters were spotted - including a half-mile-wide tornado close to Wichita.
While no injuries or deaths were reported in the town, an Air Force base and a mobile home park were badly damaged.
In the state's central-north, a tornado touched down near Tipton, taking tin off a building.
Elsewhere in Oklahoma, one twister hit Mustang, a suburb of Oklahoma City, before dawn.
There was major roof damage to at least one home, while trees, power lines and fences were down.
Tornadoes also briefly struck on Saturday afternoon in Nebraska's Nuckolls County and Thayer County, but no major damage was immediately reported.