Donte Greene had 17 points and Kristof Ongenaet added 12 for Syracuse (16-7, 6-4 Big East).
Corey Fisher hit five 3-pointers and scored 21 points for Villanova (13-7, 3-6). The Wildcats, ranked in the Top 25 for a portion of the season, are on their longest losing streak since they lost five straight toward the end of the 2003-04 season.
Villanova's last four losses have all been by double digits, and the Wildcats will surely need a big comeback in the second half of the Big East season if they want to make the NCAA tournament for a fourth straight year.
The Wildcats also lost their second game in two Saturdays at the Wachovia Center, their off-campus where they were nearly invincible the last three years. This time, they were left to watch about 2,000 Orange fans wave, taunt and cheer in the waning moments.
Harris helped the Orange pull away late when he scored five straight points, including a three-point play, that put them head 75-63.
The Wildcats had no more runs left after keep the score close earlier in the half.
Scottie Reynolds, who struggled with his shot all game, sank a jumper that pulled the Wildcats to 50-49.
Harris made two straight baskets and Ongenaet converted a three-point play that helped the Orange stretch their lead to double digits for the first time in the game.
Fisher hit a pair of 3s that sliced Syracuse's lead to 66-60. Ongenaet, though, buried a 3 at the shot clock buzzer.
Each time the Wildcats tried to rally in the second half, Syracuse was there with a hot streak of their own. The Orange shot 63 percent from the field and outrebounded Villanova 34-22.
The Wildcats reversed a trend of falling behind big early and grabbed an 11-point lead midway through the first half.
The Orange, who tried to keep pace by working the ball inside, turned to the long ball to take control the game. Greene hit a pair of 3s and Flynn sank one that sparked a 15-0 run and put the Orange ahead 39-31. They took a 44-39 lead into halftime.
The Wildcats trailed at the break for the sixth straight game.
Scoop Jardine, a Philadelphia native, returned for the Orange after serving a suspension for violating university policy. He sat out two games.