Romo was hot in the first half, completing his first 13 pass attempts as the Cowboys built a 28-7 lead.
The Dallas signal-caller finished 23-for-26 through the air for 270 yards as the Cowboys (5-4) continued their rebound from a 34-7 loss at the hands of the Eagles Oct. 30.
DeMarco Murray rushed for 135 yards with a touchdown and Laurent Robinson hauled down a pair of scoring passes for Dallas.
The Bills (5-4), meanwhile, dropped their second straight after coming into the game tied with New England and the New York Jets atop the AFC East.
Buffalo's Ryan Fitzpatrick connected on 20-of-31 pass attempts for just 146 yards and three interceptions.