Jordan Norwood and Deon Butler each caught a pair of touchdown passes before halftime in the first game between the old rivals in 18 years, giving Joe Paterno his 375th win as Penn State coach.
Fourth-year Syracuse coach Greg Robinson, his job on the line, had his record drop to 7-31.
The lopsided loss before an orange-clad crowd of 45,795 came the day after former stars Jim Brown, Floyd Little, Art Monk, Don McPherson, and 40 members of the unbeaten 1959 team attended premiere of "The Express," a movie about Ernie Davis. He was the star of that championship team and in 1961 became the first black player to win the Heisman Trophy, two before he died of leukemia.
The schools met in every season except one from 1922-90, but the series ended when the Big East was formed and Penn State joined the Big Ten. Today, the programs are headed in opposite directions and it didn't take long to see that.
Penn State (3-0) outgained Syracuse 191-5 in the first quarter, and the Orange (0-3) did not get a first down until Cam Dantley hit Grant Mayes for a 26-yard gain early in the second with Syracuse already trailing 28-0.
There was little indication this game once meant so much to Eastern football. Syracuse, a 27½-point underdog, was outgained 393-42 in the first half, getting just 4 yards on 13 rushing attempts.
Penn State, which led 38-6 at halftime, has scored at least 35 points in the opening half of all three of its games, the first time the Nittany Lions have done that since 1994.
Butler had seven catches for 110 yards and Norwood had five for 113. Daryll Clark finished 10-for-21 for 163 yards passing and two TDs, and backup Pat Devlin was 8-for-13 for 130 yards and two scores. Evan Royster had 101 yards rushing on 13 carries, his second straight 100-yard game.
Penn State, which leads the series 41-23-5, wasted no time sucking the wind out of Syracuse's sails. After fumbling the ball away at its own 36, they got the ball back on the next play when Dantley's quick pass to Curtis Brinkley in the left flat was ruled a lateral after it bounced short and was recovered by the Nittany Lions at their own 45.
Clark hit Norwood in the left flat on the next play, and he streaked untouched across the middle for a 55-yard TD reception.
Patrick Shadle kicked field goals of 44 and 52 yards for the Orange, who scored their lone touchdown late in the third. Dantley hit Donte Davis over the middle for 35 yards, then connected with Marcus Sales on an 11-yard scoring pass on fourth down.