The winning boot came after an 11-play drive led by Levi Brown, who went 3-for-5 passing during the span for 24 yards.
The Bills had Tyler Thigpen behind center for most of the second half and he went 12-for-28 for 101 yards with a touchdown and two interceptions.
Buffalo also benefited from a good performance by Ryan Fitzpatrick in the first half. The veteran went 11-for-11 to start the game and found Steve Johnson on a 52-yard TD strike.
Jacksonsville was led by David Garrard, who went 11-of-21 passing for 106 yards in the third quarter. Garrard also rushed for 9 yards and a score.
Rookie Blaine Gabbert, the Jaguars' 10th overall pick, completed 6-for-13 passes for 52 yards with a TD and an interception.