Heavy rain was already falling across the Iowa, Illinois and Wisconsin borders as of 4:30 a.m. ET, prompting a patchwork of flash flood watches and warnings from Lake Michigan into South Dakota.
Twisters were most likely to touch down in northern Illinois but were also possible in south Michigan, northern Indiana.
The "Rockford [Illinois] to Chicago area will need to be watched closely between 4 p.m. and 8 p.m. central time [5 p.m. to 9 p.m. ET]," Karins said.
The storm was likely to come in two waves, a morning cluster of thunderstorms in the Upper Mississippi and Ohio valleys followed by a single squall line pushing east across Indiana, Ohio and Michigan by the evening, according to The Weather Channel.
The forecaster added that "we can't rule out" this squall line surviving until the mid-Atlantic states on Thursday, causing wind gusts and severe weather in Washington, D.C., and Philadelphia.
It would be the second time in three days that the mid-Atlantic has been targeted by severe weather, after heavy rain, winds of up to 80 mph and golf-ball-sized hail battered the region Tuesday.