Despite the incident, the Bills won their last game of the season to finish 13–3, tied for the best record in the history of the franchise, but they lost control of their destiny to clinch the number 1 seed in the AFC as a result of the cancellation, which allowed Kansas City to clinch the number 1 seed in the AFC the day before their last game of the regular season despite having the head-to-head tiebreaker.

Stefon Diggs had 3 touchdowns on Monday Night Football and the Bills thumped the defending #1 seed in the AFC Titans 41–7 after losing to them the last 2 seasons.

The Bills responded with an 8-minute drive, but on 4th and Goal from the 1-yard line, Josh Allen's pass fell incomplete and turned the ball over on downs.

The Bills forced a Dolphins punt, but Thomas Morstead's kick hit Trent Sherfield in the buttocks and deflected backwards and out of the end zone for a safety to make the score 21–19.

With 18 seconds left, Allen avoided a sack and passed the ball to Isaiah McKenzie who tried to get out of bounds at the MIA-35 but was tackled just short of the sideline.

The Bills hustled to get back to the line of scrimmage in time, but the clock hit all zeros and players on both teams collapsed in exhaustion.

In a rematch of the previous season's AFC Divisional playoff game against Kansas City, which saw Buffalo lose in overtime after allowing the Chiefs to tie the game with just 13 seconds left in regulation, the Bills and Chiefs competed toe-to-toe on both offense and defense until the fourth quarter.

Chiefs quarterback Patrick Mahomes was intercepted by Bills cornerback Taron Johnson two plays later, preventing another last-minute scoring drive by Kansas City in addition to allowing Buffalo to avenge its playoff loss.

The Bills squandered a 14–3 first-half lead and lost to Zach Wilson and the rival Jets 20–17, thanks to a strong performance from the Jets' defense and run game (despite missing starting running back Breece Hall due to a season-ending injury), in addition to a fourth-quarter field goal by Greg Zuerlein set up by a 6-minute drive that started at New York's four-yard line.

In addition, Allen, who scored two rushing touchdowns but also threw two interceptions during the game, suffered an elbow injury on Buffalo's final drive, which ended with a turnover on downs and allowed the Jets to run out the clock.

Due to a severe lake effect snowstorm in Buffalo, this game was moved to Ford Field in Detroit in a similar fashion to the Bills' 2014 home game against the New York Jets, which was moved due to the "Snowvember" storm that dumped 7 feet of snow on Highmark Stadium.

In Buffalo's third Thanksgiving Day game in four years, Detroit, winner of three straight after a 1–6 start, kept pace with the Bills in a back-and-forth affair and took the lead in the fourth quarter.

[75] Despite the Lions tying the game with a field goal with 23 seconds left on the clock, Allen put the Bills into field goal range on the next drive with a 36-yard pass to Stefon Diggs, who was double-covered,[76] and Bass made the game-winning 45–yard kick, allowing Buffalo to win 28–25 and improve to 8–3.

Aside from a 48-yard catch-and-run touchdown pass in the first quarter from Patriots quarterback Mac Jones to Marcus Jones, who normally plays cornerback, the Bills kept New England's offense in check, forcing numerous punts, and dominated the game with a balanced offense between the passing and rushing attacks, resulting in a 24–10 win in favor of Buffalo.

Allen and the Bills offense would nonetheless adjust to Miami's heavy blitz, setting up a Dawson Knox touchdown reception with several quarterback runs to avoid pressure, with Allen barely crossing the plane on Buffalo's ensuing two-point conversion attempt to tie the game at 29.

In frigid conditions, Buffalo trailed Chicago 10–6 at halftime, partly due to Tyler Bass missing an extra point and a field goal in addition to a redzone interception by Josh Allen, but stormed back in the second half thanks to strong performances by running backs Devin Singletary and James Cook, outscoring the Bears 29–3 the rest of the way and holding dual-threat quarterback Justin Fields to just six yards rushing in the game.

[80] at Paycor Stadium, Cincinnati, Ohio The game was postponed with 5:58 remaining in the 1st quarter due to an injury to Damar Hamlin, who was sent to the hospital in critical condition after collapsing on the field.

While the Bills were widely criticized by the media for losing this playoff game in blowout fashion,[88][89] several players on the team revealed their emotional exhaustion after the game due to several events that occurred to the team and the city of Buffalo during the course of the season and offseason,[90] including Hamlin's collapse, two severe blizzards, including one during Christmas that killed dozens in Erie County,[91] owner Kim Pegula suffering "unspecified health issues" in June that were later revealed by her daughter Jessica Pegula to be cardiac arrest,[92] and the 2022 Buffalo shooting in May.

[93] Guard Rodger Saffold and safety Micah Hyde stated that the team had "run out of gas" after facing constant adversity throughout the "emotionally draining" season.