Fox fell ill while golfing in Charlotte, N.C., on Saturday and will undergo an aortic valve replacement, a surgery that had been scheduled for after the season. He is expected to be away from coaching for at least a month, team officials said.
Del Rio takes over a 7-1 team that is in second place in the AFC West behind 9-0 Kansas City. He will maintain his duties as Denver's defensive coordinator.
Del Rio coached Jacksonville for nine seasons, from 2003-11, and had a 69-73 record with two playoff appearances.
The Broncos were ranked second in yards allowed last season, but their statistics have dropped off sharply this season. They are now ranked 24th.