Indiana State Police said motorists should avoid eastbound Interstate 94 toward Michigan and into Michigan, after a tanker carrying hazardous material rolled over. The crash happened at the 24.2 mile marker, or the Burns Harbor exit, in Porter.
Sodium Hydroxide must be removed from the vehicle before it can be moved, ISP said.
Police said the eastbound lanes will remain closed for at least 10 hours.
I-94 is also closed at exit 4 in Niles, Michigan due to numerous crashes and weather, police said.
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"Our concern in Indiana is if traffic backs up into Indiana, which could result in motorists becoming stranded in arctic temperatures, creating an extremely dangerous situation for everyone," ISP said.
It's not clear when I-94 in Michigan might reopen.
Troopers are also working on crashes on Interstate 65 and I-94. White-out conditions brought traffic to a standstill on I-65 near Lowell. Many roads, as well as on and off ramps, remain snow-covered.
Multiple troopers have also been hit while working crash scenes Friday, police said.
Despite an overnight effort of treating roads and clearing out snow from area expressways, extremely low temperatures after a winter snow storm are causing slick roads across the Chicago area.
"They're bad, really bad," Lake County, Indiana resident Jim Fleeger said. "Just the road conditions are bad; 65's closed down south of here. And, then the back roads here, north and south roads, are pretty much drifted over."
Ronald Dumas was on the roads when he passed another semi crash, this one on I-65 south near the Lowell exit.
"I hate that happened south of here, you know the truck jack-knifed," Dumas said. "It's a person's life involved, you know? You can replace freight. You can't replace a person."
Some truck drivers plan to continue on the roads, as this winter's wrath keeps a steady grip on northwest Indiana.
"Well, I just got to pull back over and go to sleep and see what time they're going to stop. Get in the horse lane, man. My company does pretty good. They gave me - I don't have to deliver it until Monday, so I'm just trying to make it home for Christmas," Kenndrick Davis said.
Indiana State Police had not reported any injuries as of Friday evening.