The Missouri State Highway Patrol says almost 300 vehicles had slid off roads across the state and more than 175 crashes had been reported by late Saturday morning.
At least four people have died and scores of motorists were injured and stranded, the Missouri State Highway Patrol said.
Some roads were blocked for hours and hundreds of drivers were stranded, with Missouri troopers responding to more than 3,000 calls on Saturday afternoon.
The victims included a woman and her 14-year-old stepdaughter, whose auto slid and was hit by another vehicle about 80 miles south of Kansas City. Another woman died when her vehicle slid on US 24 in northern Missouri and was hit by an oncoming SUV.
In Kansas, the Highway Patrol said a 62-year-old man died after his pickup truck skidded on the Kansas Turnpike and hit a concrete barrier.
The tri-state area of Indiana-Kentucky-Ohio is under a winter storm warning, with many areas already declaring a snow emergency before the storm is expected to hit on Saturday, according to Fox 19 in Cincinnati.
As the system moves eastward, it will hand off to a second coastal storm on Sunday that will bring 2 to 4 inches (5 to 10 cm) of snow to the Washington, D.C., area before it moves off the coast that night, Walker said. "St. Louis is seeing its worst snowstorm in five years".
The weather system, which started as rain from Mexico but has since turned into snow, is forecast to affect an 2,900 km swath of the United States from Colorado to the Mid-Atlantic.
The National Weather Service says snow was to begin about 3 p.m.in southwestern IL and spread northeast throughout the evening, reaching the Chicago area by early Saturday.
A mass email from Chancellor Robert Jones went out to students around noon Friday, noting that the National Weather Service had issued a winter storm warning for much of IL that extends well into the weekend. Major cities in the zone, including St. Louis, could get more than 6 inches of snow.
St. Louis Lambert International Airport spokesman Jeff Lea says airlines are canceling dozens of flights through Saturday morning.
Winter storm continues into Saturday
There is a slight chance for a few flurries on Monday, otherwise a dry week with milder weather returning on Tuesday. However, area counties had some snow and freezing rain in the December storm that caused schools to cancel classes.