The Houston Texans, who own the league's worst record at 2-11, fired coach Gary Kubiak on Friday.
Expected by some to contend for a Super Bowl berth this season, the Texans rallied to win their first two games but have lost a franchise-record 11 straight since.
Owner Bob McNair said defensive coordinator Wade Phillips will serve as interim coach.
"This has been a very disappointing year," McNair said. "We started with such high hopes. To have this string of losses is unacceptable.
"We normally would wait until the end of year to evaluate our staff; under these extreme circumstances thought best to start the process now."
Kubiak's health also has been an issue this season. He suffered a transient ischemic attack, or "mini-stroke," on Nov. 3 while walking off the field at halftime of the Texans' 27-24 loss to the Indianapolis Colts. He returned to the team after missing one game.
Houston endured its latest loss Thursday night, falling to the Jacksonville Jaguars 27-20, a game in which the Texans committed 14 penalties for 177 yards. The Texans have set an NFL record with seven straight losses by seven points or less, according to the Elias Sports Bureau.
"What's taken place with this organization is unacceptable,'' general manager Rick Smith said. "We've got three weeks of an evaluation process left and we've got to right the ship.'"
Kubiak, 52, was in his eighth season, having coached the Texans since 2006. He posted a 61-64 record with the franchise. He was the fourth-longest tenured coach in the league, behind Bill Belichick, Marvin Lewis and Tom Coughlin.
"I want to thank Bob McNair and his family for giving me my first head coaching opportunity in the National Football League," Kubiak said in a statement. "Bob has treated me with the utmost class and respect throughout my career with the Texans. I am appreciative of him for bringing me back to Houston to coach my hometown team.
"I want thank the players and coaches for all the work they have put in during my years with the Texans. Though we came up short this season, the work, effort and sacrifice they gave me and this organization over the last eight seasons is not to be taken for granted. I want to wish them all the best."
The first head coach to lose his job this season, Kubiak was on the hot seat following the 2010 season as well, when the Texans went 6-10. However, he rewarded McNair and general manager Smith for their patience in him, guiding the Texans to back-to-back AFC South titles the next two seasons and winning the league's coach of the year award in 2011.
McNair said the decision to fire Kubiak -- who signed a contract extension through 2014 last season -- was a hard one.
"It was difficult for me because I think so much of Gary,'' McNair said. "We're here to have a winning culture and this year has not contributed to that.''
The roster seemed to be in place to make a run in 2013 after the Texans sent an AFC-high nine players to the Pro Bowl after last season. The club features a top-level running back in Arian Foster, two of the game's better defenders in J.J. Watt and the oft-injured Brian Cushing, a solid left tackle in Duane Brown and a still-effective Andre Johnson at wide receiver.