Iguodala took advantage of the absence of Horford to score 27 points, and Philadelphia dominated near the basket to beat the Atlanta Hawks 109-94 on Sunday.
The 76ers, who have their first four-game winning streak of the season, scored 56 points in the paint and had a combined 49 points by their starting forwards. Thaddeus Young added 22 points and nine rebounds for Philadelphia.
"It seems like we're getting it together a little bit," said 76ers guard Andre Miller, who had 19 points.
Iguodala is averaging 22.3 points the last six games as the 76ers have regained momentum after losing Brand for a month to a dislocated shoulder on Dec. 17.
"We felt we had a chance to come in and steal a win," Iguodala said. "They had two tough losses against Orlando the last two games for them. So we just tried to come out and establish ourselves early and keep it going throughout the game."
Horford, Atlanta's second-year center, sustained a bone bruise on his right knee in Friday night's loss at Orlando. He won't be with the team for its three-game road trip that begins Tuesday in Phoenix.
Joe Johnson, who led the Hawks with 25 points, refused to blame the loss on Horford's injury.
"It's part of the NBA," Johnson said. "There are going to be injuries. That's not an excuse for why we're losing. We're just not playing with energy at the start of the game."
The Hawks, who won nine of their last 10 games in December, have lost three straight games, including the humiliating 121-87 loss in Orlando on Friday.
Philadelphia scored the first 10 points. Atlanta fought back but trailed after the opening minutes of the second period.
"I think Orlando took some starch out of us a little bit," Hawks coach Mike Woodson said. "We're not competing defensively like we have been, and that's on me. I've got to get them back playing defense because that's the only chance we have of winning."
Slow starts have become a disturbing trend for the Hawks.
"It's a big concern because we just don't have any energy at all," Johnson said.
Woodson said his players "are kind of in a rut right now" and "kind of looking over their shoulders a little bit."
Iguodala and Young each had two baskets in the opening 10-0 run, and Iguodala's second dunk of the first three minutes pushed the lead to 12-3.
"We controlled the pace of the game for most of the game," said 76ers coach Tony DiLeo. "Right from the beginning we got out on the break, and I thought we established that."
Rookie forward Marreese Speights had 12 points and eight rebounds.
While the 76ers scored near the basket, the Hawks leaned on their perimeter game. Mike Bibby had 22 points.
The Hawks trailed 95-90 following a basket by Johnson, but Speights scored after his offensive rebound to start an 8-0 run that pushed the lead to 103-90.
"I think both teams were a little tired," Miller said. "We were able to fight through it and get some easy baskets off their turnovers. That was a big part of the game."
Atlanta held its last lead at 35-32 early in the second period before former Hawks guard Royal Ivey's 3-pointer tied the game and started a 9-0 run which gave the 76ers the lead for good.
The 76ers took a 39-24 advantage in rebounds. ... Horford wore a sleeve on his right knee as he was not in uniform but sat on the bench. He said he was injured on an awkward landing following a rebound. ... Zaza Pachulia started for Horford but had only four points and six rebounds. ... The 76ers made 62.9 percent of their shots in the first half -- a high mark for Atlanta opponents this season -- and shot 54.7 percent for the game.