Whisenhunt was 3-20 as head coach in Tennessee, including 1-6 this season. Only one coach in NFL history had was worse in his first 23 games with a team (John McKay, 0-23 from 1976-78).
"I'm grateful for the opportunity and appreciate the hard work the staff put in and the support I got from our players and our fans," Whisenhunt said. "I wish the organization much success going forward."
The Titans lost their sixth consecutive game Sunday at Houston. It's the third straight season Whisenhunt lost at least six in a row as a head coach.
"After thoughtful consideration, the decision has been made to relieve Ken Whisenhunt of his head coaching duties," said Titans controlling owner Amy Adams Strunk. "We have expected more progress on the field, and I felt it was time to move in a different direction. I would like to thank Ken for his efforts with our team, as he worked very hard to try to move us forward."
The move is the first significant action from the front office and ownership since the death of Bud Adams, who died in October 2013. Adams Strunk made the decision.
Mularkey was hired by Whisenhunt as tight ends coach in 2014 and was promoted to assistant head coach this past offseason. He has three previous years of head coaching experience: two years with the Buffalo Bills (2004-05) and one year with Jacksonville (2012). He had eight seasons as offensive coordinator in the NFL prior to that with the Steelers, Falcons and Dolphins.
In three of his four seasons running the Falcons offense, the team produced a 3,000-yard passer, 1,000-yard receiver and 1,000-yard rusher in the same season.
Mularkey played tight end in the NFL and totaled 114 games played during his nine-year career with the Minnesota Vikings and Steelers.