Blizzard conditions and flooding closed numerous roadways in the region. Nearly 1,400 flights were canceled at Denver airport, where all runways were shut down.
Colorado declared a state of emergency and National Guard troops were activated.
National Guard troops in Nebraska were put on alert for possible activation, as emergency officials braced for the storm to intensify overnight there.
"This has the potential to be a very severe weather event," Nebraska Governor Pete Ricketts said.
"We're already seeing flooding in a number of communities and evacuations in several communities."
Colorado was walloped by heavy snow and high winds gusting to as much as 90 miles per hour -- leaving hundreds of thousands of people without power, according to the Denver Post.
Schools, businesses and government facilities were closed in Wyoming, according to the Wyoming Tribune Eagle, which itself was forced to shut down because of the weather.
Officials in Nebraska said they expected flooding there to worsen -- potentially to record levels.
"It is an unprecedented event today," said Kyle Schneweis, Nebraska's director of transportation.
"Just today we're facing blizzards, white-out conditions, flooding, dense fog, and each of those pose a unique risk," he said.
An area north of Omaha was evacuated as floodwaters topped a levee, according to television station KETV.
The National Weather Service also predicted river flooding from rain and snowmelt in parts of Iowa, which could last into the weekend.
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