Dwayne Anderson scored 17 points for the third-seeded Wildcats, who responded to Pittsburghs physical play by sinking 22 of 23 free throws in the East Regional final.
Villanova (30-7) will play the winner of the South Regional championship between North Carolina and Oklahoma. The Wildcats are the lowest-remaining seed in the NCAA tournament, though not quite as big an underdog as the eighth-seeded 85 team that was the lowest seed ever to win it all.
Sam Young scored 28 and DeJuan Blair had 20 points and 10 rebounds for Pittsburgh (31-5), the first No. 1 seed to leave the brackets this year.
It was physical. It was defensive. It was ugly.
Just the way they like it in the Big East, which will send a second team to Detroit with a chance at a third when Louisville plays Michigan State in the Midwest Regional final on Sunday.
With big bodies clogging the lane and 3-pointers clanging off the rim, the teams pushed and shoved their way through the first 35 minutes before they started making baskets and making plays. The lead changed 15 times six of them in the last six minutes, before Pittsburghs Levance Fields hit a pair of free throws with 5.5 seconds left to make it 76-all.
Reggie Redding, who threw the ball away trying a full-court pass on the previous inbounds play, got it to Dante Cunningham this time, and he dished it to Reynolds. The Villanova guard weaved his way into the lane for a falling-down floater in traffic.
The clock expired, and the Wildcats celebrated. But the officials immediately moved to put a half-second back on the clock.
Fields took the inbounds pass and launched a 65-footer that hit the backboard but then bounced harmlessly to the floor.
Villanova coach Jay Wright went first to hug his wife and kids, then made his way to Rollie Massimino to share the moment with the last Wildcats mentor to reach the Final Four. That team beat Georgetown in an affair that was dominated by the Big East St. Johns also made it just like this years weekend in Detroit promises to be.
Connecticut advanced to the national semifinals earlier Saturday, so it was already certain that at least half of the Final Four would come from the Big East.
Reynolds was picked the most outstanding player of the regional.
Villanova, which beat Pitt back in January, got there in a way that would make the big, bruising Big East proud.
Pittsburgh guard Jermaine Dixon left for most of the second half after landing awkwardly in the splits before Villanovas Shane Clark landed on his left leg.
Blair played the second half blood stains from an unknown victim streaking his shorts. Two Pitt players came over the first-row press table during the game, sending monitors and telephones and a pair of New York sports writers a-skitter.
The Panthers played Steelers-style basketball, but every time they sent Villanova to the line the Wildcats calmly sank them until Redding missed with a chance to make it a five-point game with 20 seconds left. Blair scored on a layup with 13 seconds to go, and then Redding tried a full-court inbounds pass that Dixon gathered in.
Fields sank two free throws to tie it the 10th tie of the game.
Villanova held Pitt to one basket in the first 4:59 and opened a 10-3 lead, making it 22-12 midway through the first half before the Panthers scored eight straight. Fields got it started with a 3-pointer, and Blair cut it to two points on a three-point play with just under eight minutes remaining.
Pitt trailed by three with several chances to tie it before Fields stepped back and hit a 3-pointer the mirror-image of his game-winning shot from the regional semifinal over Xavier to make it 30-all with 1:50 left in the half. After trading free throws, Young hit a pair with 4 seconds left to give Pittsburgh a 34-32 halftime lead.