Monday Night Football was a matchup of AFC East rivals, the New England Patriots and Buffalo Bills.
New England was a 14-point favourite, but the Bills' defence held the Pats to just four field goals through 3-plus quarters before they pulled away late and won 25-6.
Devin McCourty returned an interception of a Derek Anderson pass 84 yards for a touchdown in the fourth quarter to break the game open.
New England quarterback Tom Brady was 29 of 45 for 324 yards but was held without a touchdown pass for the first time this season.
In the Belichick-Brady Era, the Patriots are now 32-5 against Buffalo.