Pierce had 31 points and 11 rebounds and Antoine Walker scored 20 points as the Boston Celtics overcame Iverson's return to defeat the 76ers, 92-82, in Game One of their Eastern Conference first-round series.
Iverson missed the final 14 games of the regular season after suffering a broken hand against Boston on March 22. He looked like the reigning the Most Valuable Player in the first quarter, but Pierce played like a candidate for the award thereafter.
Iverson scored Philadelphia's first four points, nailing a jumper just four seconds into the game before sinking a pair of free throws 66 seconds later. He scored 15 points on 4-of-6 shooting in the first 12 minutes, but Pierce was nearly as impressive.
Pierce scored nine points in the opening period and completed a three-point play to erase the Sixers' final lead and forge a 28-28 tie with 20 seconds left. Walter McCarty nailed a half-court shot to beat the first-quarter buzzer and give the Celtics lead for good.
"I knew it was going to be on track but I didn't know it was going to go in," McCarty said. "It really lifts the team up and gives us a little bit of momentum."
Iverson, who did not start the second quarter, could not regain his form after returning with 8:30 remaining in the first half. He missed his final nine shots and finished with 20 points, making just five free throws in the final three quarters.
"I just missed shots," he said. "I took a couple of bad shots that were really contested. For the most part, I felt like I took shots that I can make. I just didn't knock them down, for whatever reason. It didn't have anything to do with the hand or the defender or anything. I just missed shots. That's part of the game."
"I thought it was a miracle he's out there," Sixers coach Larry Brown said. "He hasn't practiced. I thought he tried awful hard. He made some shots early and couldn't make anything late. I think our team deferred to him. We seemed to figure that he was going to win it for us."
The third-seeded Celtics led by as many as 11 points twice in the second quarter and had a 55-51 edge 2:14 into the third quarter before Pierce scored the first seven points during an 11-2 run. He sank a 15-footer and followed with a tip shot before draining a 3-pointer with 6:59 to go.
"I told our coaches (the Celtics) are ready to blow this thing out. We've got to get control," Brown said. "Then we come out in the third quarter and we self-destructed. Give them credit. They did a great job of getting the ball to the right people."
Boston had a 66-53 edge after the spurt and cruised to its first playoff victory since Game Two of its first-round meeting with Orlando in 1995.
In his first playoff game, Pierce made 10-of-25 shots from the floor, including 3-of-8 3-pointers, and was showered by chants of "MVP!" in the final minutes from the crowd at the FleetCenter, which was hosting its first postseason game.
"I thought knew what playoff basketball really was, but I didn't know until I stepped out on that court," Pierce said. "It sent chills through my body to hear the whole crowd chanting MVP."
Also in his first postseason game, Walker made 8-of-23 shots and grabbed seven rebounds. He made 2-of-4 3-pointers as the Celtics went 8-of-18 from beyond the arc, tying a pair of franchise playoff records.
"You really have to be a part of our basketball team to understand the impact on everything that we do," Boston coach Jim O'Brien said. "We're blessed to have great leadership from our captains, but Antoine has a real sense of the game and what we're trying to accomplish. He's a very big reason that we find ourselves where we are right now."
McCarty scored 14 points off the bench as Boston saw its reserves outscore Philadelphia's, 23-15.
Matt Harpring had 18 points and eight rebounds and Eric Snow and Aaron McKie scored 11 points apiece for the sixth-seeded Sixers, who lost Game One of their first-round series for the second straight season.
Dikembe Mutumbo had nine points and 11 rebounds and Derrick Coleman added nine and 10 for Philadelphia, which held a slight 44-39 rebounding edge but shot just 38 percent (27-of-71).
The Sixers committed 18 turnovers leading to 19 points for the Celtics. Snow and Iverson, Philadelphia's starting backcourt, combined for eight turnovers.
"They played better than us, today. It's simple as that," Iverson said. "We know we can beat this team and we know that they're obviously capable of beating us. They had a better game than us. We just couldn't get anything going offensively and we couldn't stop them defensively. That's just how the game goes sometimes."
Game Two of the best-of-five series is Thursday in Boston. This is the 18th playoff series between the rival franchises but the first since 1985.
"This game is behind us, we've got to stop thinking about it and go into practice thinking about game No. 2," McCarty said. "We've got this one under our belt, now we've go to move on."