Blount carried the ball 24 times and also provided two long kickoff returns to set up two scores as New England (12-4) overcame wet, rainy conditions to secure the AFC's second seed and a first-round bye.
Tom Brady completed 14-of-24 passes for 122 yards with a touchdown for the AFC East champs.
Julian Edelman hauled down nine passes en route to 65 yards.
Backup Thad Lewis threw for 247 yards with a TD on 16-of-29 efficiency for the Bills (6-10).
C.J. Spiller compiled 105 yards on 19 carries.