[1][2][3] The Bills had fired head coach Dick Jauron after Week 10 of the 2009 season; he had been replaced on an interim basis by defensive coordinator Perry Fewell.
The Bills held an open competition for the starting quarterback position between Trent Edwards, Ryan Fitzpatrick and Brian Brohm during training camp.
He was only to be traded to the Seattle Seahawks after four games into the regular season with the rise of running backs Fred Jackson and first-round draft pick C. J. Spiller created a logjam.
Nine of the Bills' twelve losses were to teams that qualified for the postseason, including both representatives in Super Bowl XLV – Pittsburgh and Green Bay.
The final score was made when long snapper Garrison Sanborn snapped the ball to Brian Moorman out of bounds for a safety, giving the Dolphins 2 more points and the Bills a loss.
In the 1st quarter Buffalo trailed early as kicker Mason Crosby made a 44 and a 24-yard field goal, followed by RB Brandon Jackson getting a 1-yard TD run.
The Bills replied in the second quarter with Lindell making another 39-yard field goal, which was followed by QB Ryan Fitzpatrick getting a 5-yard TD pass to RB C. J. Spiller.
The Bills fell further behind in the third quarter when Brady found Moss again on a 35-yard TD pass, but straight after the PAT, Buffalo scored when C. J. Spiller returned a kickoff and ran 95 yards to the endzone for a touchdown.
Still looking for their first win of the season, the Bills went home, donned their throwback uniforms, and played a Week 4 AFC East duel with the New York Jets.
New York would add onto their lead in the second quarter as kicker Nick Folk nailed a 19-yard field goal, followed by quarterback Mark Sanchez completing a 41-yard touchdown pass to wide receiver Braylon Edwards.
Buffalo would close out the half as quarterback Ryan Fitzpatrick connected with tight end David Martin on a 4-yard touchdown pass.
The Bills would close out the game in the fourth quarter as Fitzpatrick completed a 13-yard touchdown pass to wide receiver Stevie Johnson.
In the first quarter the Bills took the lead as QB Ryan Fitzpatrick made a 45-yard TD pass to WR Lee Evans; followed by kicker Rian Lindell making a 29-yard field goal.
But they pulled ahead with QB Ryan Fitzpatrick completing a 33-yard TD pass to WR Lee Evans, followed by kicker Rian Lindell hitting a 21-yard field goal.
The Bills managed to tie the game in the 4th quarter with Fitzpatrick making a 17-yard TD pass to Evans, and with Lindell getting a 50-yard field goal.
The decision was made with Succop successfully hitting a 35-yard field goal with 3 seconds left on the clock to keep the Bills winless after 7 games.
Buffalo took the lead in the fourth quarter with a 1-yard touchdown run from fullback Corey McIntyre (with a failed two-point conversion), but the Bears got the last laugh with Cutler completing a 2-yard touchdown pass to wide receiver Earl Bennett, along with a two-point conversion pass to running back Matt Forté.
The Lions tried to come back in the 4th quarter with Rayner making a 45-yard field goal and with QB Shaun Hill throwing a 20-yard TD pass to WR Calvin Johnson.
Ryan Fitzpatrick matched his career high with four touchdown passes during Buffalo's biggest comeback in 13 years, and the Bills won their second consecutive game Sunday, 49–31 over the bumbling Cincinnati Bengals.
Buffalo (2–8) took advantage of Cincinnati's depleted secondary—Joseph and safety Chris Crocker went out late in the first half—for its biggest comeback since it overcame a 26–0 deficit and topped the Indianapolis Colts 37–35 on Sep 21, 1997, according to STATS LLC.
Coming off their win over the Bengals, the Bills went home, donned their throwbacks, and played a Week 13 intraconference duel with the Pittsburgh Steelers.
The Bills answered in the third quarter as quarterback Ryan Fitzpatrick found running back Fred Jackson on a 65-yard touchdown reception.
It featured Bills LB Arthur Moats' hit on Vikings QB Brett Favre, which would end the longest streak of quarterback starts in NFL history at 297 games.
Hoping to snap a two-game losing streak the Bills played on home ground for an AFC duel against the Browns.
The Bills trailed early as kicker Phil Dawson got a 19-yard field goal, but they took the lead in the second quarter as QB Ryan Fitzpatrick completed an 11-yard TD pass to WR David Nelson.
Coming off their win over the Browns the Bills flew south to Sun Life Stadium for an AFC East rivalry rematch against the Dolphins.
The second quarter saw the Bills taking the early advantage with QB Ryan Fitzpatrick completing an 18-yard TD pass to WR David Nelson.
The lead was narrowed in the fourth quarter with QB Chad Henne getting a 9-yard TD pass to WR Brandon Marshall, but the Bills defense was solid enough to hang them on for the win.
Their offense struggled as CB Marquice Cole returned an interception 35 yards for a touchdown, which was then followed by QB Mark Brunell making a 17-yard TD pass to WR Santonio Holmes.
The Bills made their only score of the game with FS Jairus Byrd returning an interception 37 yards for a touchdown, but they fell further behind after Brunell found WR Braylon Edwards on a 52-yard TD pass.