McDermott, 51, went 98-50 in the regular season with eight additional playoff wins and eight losses in nine seasons as coach of the Bills.
His final game was another postseason heartbreaker, losing 33-30 in overtime in Saturday’s divisional-round playoff contest at Denver.
“Sean has done an admirable job of leading our football team for the past nine seasons,” team owner Terry Pegula said in a statement.
“But I feel we are in need of a new structure within our leadership to give this organisation the best opportunity to take our team to the next level. We owe that to our players and to Bills Mafia.”
Buffalo also promoted general manager Brandon Beane to president of football operations. He will lead the search for a new coach as the Bills prepare to move into their new stadium in 2026.
“Brandon will oversee all facets of our football operation,” Pegula said. “… I have full faith in and have witnessed Brandon’s outstanding leadership style and have confidence in his abilities to lead our organisation.”
Beane, 49, was hired as the general manager in Buffalo in 2017.
McDermott led the Bills to five consecutive AFC East titles from 2020-24 while winning at least 10 games in each of the past seven regular seasons (12-5 in 2025).
He ranks second in franchise history in coaching wins behind Hall of Famer Marv Levy (112).
McDermott and quarterback Josh Allen never reached a Super Bowl, however.
The Bills held a 27-23 lead in the fourth quarter against the Broncos in the divisional playoff defeat on Saturday.
It was their fourth playoff loss since 2022 when leading in the fourth quarter. Buffalo was 0-3 in playoff overtime games under McDermott.
“Sean helped change the mindset of this organisation and was instrumental in the Bills becoming a perennial playoff team,” Pegula said in his statement.
“I respect all the work, loyalty and attention to detail he showed for this team and the community.”
A couple of Buffalo players, defensive tackles Jordan Phillips and DaQuan Jones, expressed their displeasure with the firing on Instagram.
“This s*** here is so stupid honestly sickening,” Phillips posted. “The best coach I’ve ever been around.”
Added Jones: “Don’t make sense but ya got what ya wanted.”
The Bills are the 10th team to make a coaching change this season. The New York Giants hired John Harbaugh and Kevin Stefanski was named head coach of the Atlanta Falcons, leaving eight vacancies.
McDermott could emerge as a candidate to fill one of the remaining openings in Arizona, Baltimore, Cleveland, Las Vegas, Miami, Pittsburgh or Tennessee. (Reuters)
