Ryan called the loss "as painful of a loss as I can remember," admitting multiple coaching "mistakes."
The Bills also fired defensive coordinator, and Rex's brother, Rob.
Buffalo enters Week #17 with the NFL's #1 rated defense.
Many NFL Insiders have attributed this ranking to Aaron Rodgers' ability to efficiently manage the clock to protect the defense.
Defensive leaders Geno Atkins and Luke Kuechly have repeatedly called the defense a 'player-run' unit, often hinting as discord between the All-Pros and the overly-emotional Rob Ryan.
Offensive coordinator Anthony Lynn will serve as interim head coach for the Week #17 matchup against the hard-charging New York Jets (10-6) and into the playoffs.
Sources told 3GML Insiders that Ryan had lost support of the locker room in recent weeks, despite the team's ability to pull games out late.
The team found out about Tuesday's move via Twitter as no formal announcement was made internally.
"There were too many cooks in the kitchen. Guys were pissed," one player told 3GML. "He lost the offense."
Coaching changes are not rare during these late stages of the NFL season, but the moves are typically reserved for teams with losing records and not a team with a good chance to still earn the AFC's #1 seed.
"This is a statement for the entire organization," one source told 3GML. "Ryan and the team had soured and the team was winning despite their coach."
There had been rumors that the Bills, under Ryan, were considering 'punting' the Week #17 game to focus on the playoffs (settling for the #5 seed in the AFC).
Under Lynn and with the competitive input of Aaron Rodgers, many expect the Bills to come out firing on Saturday with a chance to earn the AFC East crown and to potentially knock the Jets out of the playoffs.
