In his first game at AT&T Stadium since suffering a career-threatening ankle injury on the same field a year ago, Prescott was in fine touch as the Cowboys dominated the Eagles from start to finish.
The quarterback went 21 from 26 for 238 yards without an interception as Dallas took top spot in the NFC East with their second win from three games.
Ezekiel Elliot ran for 95 yards and made two touchdowns while tight end Dalton Schultz had the first two-touchdown match of his career.
The Cowboys were on the scoreboard after just three minutes when Elliott crossed from a yard out after a six-play 75-yard drive.
Philadelphia struck back to make it 7-7 minutes later when Prescott was stripped and fumbled in the end zone as Fletcher Cox pounced on the ball for the touchdown, but Dallas led 14-7 after Prescott hit a wide-open Schultz late in the first quarter.
The Cowboys enjoyed a 19-1 advantage in first downs late in the first half though led only 20-7 at the long break, but soon pulled away when Trevon Diggs ran for a touchdown on the third play of the second half.
Two more touchdowns from Cedrick Wilson and Schultz made it 41-14 deep in the last quarter before a consolation score from the Eagles' Greg Ward.