Eyewitness video showed armed police conducting a search in a nearby neighbourhood just after the suspect was killed.
The rampage began around 5 p.m. local time (000GMT) when the gunman, who has not been publicly identified, shot and killed two women and wounded a man near downtown Denver, Police Chief Paul Pazen said at a news briefing.
The gunman then drove into the neighbouring city of Lakewood, where he shot and killed a fourth person inside an unspecified business, Lakewood police said. He then entered a local hotel and shot and wounded a clerk and police officer.
The suspect was eventually shot dead by police.