The Buffalo Bills concluded their regular season with a disappointing 23-16 loss to the New England Patriots, who ended the season with a 4-13 record. This defeat, however, might benefit the Bills in the long run as it hindered the Patriots from securing the top pick in the upcoming draft. The Patriots' win also led to the dismissal of head coach Jerod Mayo shortly after the game.

Despite the loss, the Bills found some positives. With most starters resting, they avoided injuries. Quarterback Josh Allen extended his consecutive starts streak to 115, while James Cook tied a franchise record for rushing touchdowns in a season. The Bills also made history by becoming the first team to score both 30+ rushing and receiving touchdowns in a season.