Their fellow Americans Dufner and Perez made it tight with a closing 68 but Dufner came up short with a 14-foot putt at the last which would have forced a tie.
South Africans Charl Schwartzel and Louis Oosthuizen were third at 20-under 268 after carding a 62 but overnight leaders Kevin Kisner and Scott Brown soared to a 77 and slumped to a share 15th.
"The key to this is Billy's putter," Piercy told PGA Tour radio. "It really was. He rolled it amazing all week."
Horschel's 2013 win was his first on the PGA Tour, but he said Sunday's triumph also meant a lot.
"You never want to let a team mate down and to feel you helped out the team to victory, that was huge," said Horschel of winning his fifth tour title, one better than Piercy's career tally of four.
The pair started the day three shots back, but picked up shots at the first two holes and another at the seventh before seizing the lead with back-to-back birdies at 10 and 11 before finishing up with seven consecutive pars.
"I knew if we were going to have a chance to win, I was going to have to make some putts and I knew I was going to have to make some par putts," Horschel said.
"It was nice to feel comfortable that I was going to make it."
Dufner and Perez also were bogey-free with four birdies but their last came at the 11th and they were unable to make a push for victory over the final seven holes.
Kisner and Brown, one-stroke leaders to start the day, fell apart on the back nine with three bogeys and a double-bogey after making the turn at even par following two bogeys and a pair of birdies.
Michael Kim and Andrew Putman, who led after the second round, also had their troubles with three consecutive bogeys to start the back nine and a double-bogey at the par-four 15 to shoot 76 and also tie for 15th.
(Reporting by Gene Cherry in Raleigh, North Carolina, editing by Ed Osmond)
