The crash occurred on Interstate 70 in the Denver area Thursday evening, according to the Lakewood Police Department. It tweeted that there were "multiple" fatalities, but did not provide the number of people killed, saying authorities are working to put out the fire and match the victims to their vehicles.
The priority now is to extinguish the blaze and identify who was in each car, police said. At least six people were transported to hospitals.
The I-70 eastbound traffic was at a standstill because there was another crash farther up the freeway, police said at a news conference. Authorities said the semi rammed into the cars stuck in the traffic from the other crash.
Video from the scene showed firefighters spraying water on towering orange flames and burning cars.
"This is looking to be one of the worst accidents we've had here in Lakewood," Countryman said.
The Denver West Parkway bridge over I-70 got significant structural damage from the fire, authorities said. Both directions of I-70 are closed overnight at the scene of the fire, police said.