Temple (6-2) trailed by one, 36-35, at the half but slowly wore down the Wildcats (5-4), who have lost four of their last five. The Owls have won three straight.
Temple outscored Villanova 43-31 in the second half to seal it.
"I think every year our fans are excited to play Villanova," said Moore, who scored 23 of his points in the second half. "It makes it even better when we win."
Temple, which was without starting 6-foot-10 center Micheal Eric (right knee), overcame Villanova's size advantage.
"They were the better team tonight," Villanova coach Jay Wright said. "They made more plays. They're not spectacular, but they are the type of plays that win games."
With 8:46 left in the game, Villanova tied it at 54-54 on a layup by James Bell. Temple responded with a 10-0 run that ended with a Moore jumper with 6:18 left, and Villanova failed to get within seven points the rest of the game.
The teams were knotted 39-39 in the rebounding battle, but the Owls forced 17 Wildcats turnovers.
"I think (Villanova) got in foul trouble early and I think the opportunity presented itself to go to the basket," Moore said. "I think it was the 11-minute mark that we were in the penalty and hopefully get some calls. That 10-0 run was big, and we knew we just had to hold them tonight."
The Owls will try to make it four straight wins when they play at Texas next Saturday. The Wildcats (5-4) take on Boston University Tuesday night at home.