Major flight delays and cancellations are likely in Chicago and Detroit Thursday night and Friday.
A heavy rate of snow will clog streets and highways in the Interstate 80, 90 and 94 corridors in the Midwest.
Major disruptions to daily activities are likely with the potential for numerous school cancellations.
Snow may fall for 24 hours in some locations.
A high-impact snowstorm will slam areas from eastern Iowa to southern Ontario with a heavy accumulation to end this week.
Fresh snow will also cover areas from northern Pennsylvania and New York state to northern New England on top of the 2-14 inches of snow and ice that fell on Wednesday and Wednesday evening.
Heaviest snow to fall from Chicago to Detroit
The storm is likely to bring the single-biggest accumulation to Chicago and Detroit, where 6-12 inches of snow is forecast to fall over a 24-hour period. Locally higher amounts of snow may occur.
The snowstorm will stay south of Minneapolis and north of St. Louis and Kansas City, Missouri; Evansville, Indiana; Cincinnati and Columbus, Ohio; and Pittsburgh.
Heavy snow began to fall on parts of central and eastern Montana during Wednesday night. Flurries will streak eastward and evolve into steadier and heavier snow through Friday.
Flurries will evolve into steadier, heavier snow across a large part of South Dakota, northern Nebraska and northwestern Iowa during Thursday.
The snow will spread across southern Wisconsin, northern Illinois, northern Indiana, northwestern Ohio and the southern part of the Lower Peninsula of Michigan during Thursday night.
Ripple-effect flight delays, changes and cancellations may occur across the nation as crew and aircraft are displaced due to the impact on the major airports at Chicago and Detroit.
Few inches of snow to fall on part of northeastern US
The intensity of the snow will be much less in the Northeast, when compared to the Midwest. This snowfall is also projected to stay north of Philadelphia, New York City and Boston.
However, since the snow will fall over a broad area of the northern tier, motorists traveling long distances should expect to lengthen their trip by several hours to navigate slippery and snow-covered roads.