The U.S. Postal Service took the rare step of suspending mail delivery across much of the region.
"Through late week, expect frigid temperatures, bitterly cold and life-threatening wind chills, likely leading to widespread record lows and low maximum temperatures from the Upper Midwest to the Great Lakes and Ohio Valley".
In Chicago, Illinois, temperatures were still dropping after plunging early Wednesday to minus-19 degrees, breaking the day's record low set in 1966.
"These [conditions] are actually a public health risk, and you need to treat it appropriately", Chicago Mayor Rahm Emanuel said Tuesday. "They are life-threatening conditions and temperatures".
After sunset Wednesday, temperatures were to drop again, sinking so low that the record for Chicago - 27 degrees below zero - could be reached.
While the adjustment could be hard, not many people will miss the cold after at least 160 record lows were set throughout the Midwest and Northeast in recent days.
Wind chill attempts to quantify the effect in terms of how it feels on our skin, which is why you'll sometimes hear it called the "feels like" temperature.
Unlike most Chicago residents, Gilbert was required to report to his job at a Starbucks branch on a downtown street largely devoid of its usual bustle of people and traffic.
"I have two shirts on". Elsewhere, a man was struck by a snowplow in the Chicago area, a young couple's SUV struck another on a snowy road in northern in and a Milwaukee man froze to death in a garage, authorities said.
Thousands of flights have been canceled along with dozens of train services - a lot of them in and out of Chicago.
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More than a thousand flights, close to two-thirds of those scheduled, were cancelled on Wednesday into or out of Chicago O'Hare and Chicago Midway worldwide airports.
Mail delivery has also been suspended in places like Michigan, Missouri and in until temperatures rise.
"We have some unsafe wind chills", Andrew Orrison, a forecaster for the National Weather Service, said.
That's cold enough to cause frostbite in half an hour.
Illinois, Michigan, and Wisconsin implemented emergency measures. Customers were connected to other mains to keep water service from being interrupted, Detroit Water and Sewerage spokesman Bryan Peckinpaugh said.
Officials throughout the region were focused on protecting vulnerable people from the cold, including the homeless and seniors.
Burke Patten, spokesperson for homeless shelter provider The Night Ministry, said some of the homeless were reluctant to go to shelters. "Here we are going right into spring-like temperatures".
More than 2,500 flights were canceled across the United States, according to FlightAware. Several families who meant to leave for Pennsylvania stood in ticket lines at Chicago's Union Station only to be told all trains were canceled until Friday.
"Due to extremely high demand for natural gas with these record low temperatures and a facility incident, Consumers Energy has asked that everyone who is able to turn down their thermostats through Friday at noon so we can all get through this with minimal harm", Michigan Governor Gretchen Whitmer said in a statement.
Heavy snow was forecast in the northern stretches of ME and snow squalls predicted for other parts of the east coast.