The Clippers lost shortly after acquiring forward Zach Randolph and guard Mardy Collins from the New York Knicks for Cuttino Mobley and Tim Thomas.
Los Angeles wasted a six-point lead with 2:50 left in the game. Andre Iguodala converted a three-point play and Andre Miller hit a 3-pointer to get the Sixers within one.
Then Brand, who bolted the Clippers and signed a free-agent deal with the Sixers, nailed the winner.
Brand played his first game against the Clippers since signing a five-year deal worth around $80 million in July. Brand grabbed a franchise-record 4,710 rebounds and scored 9,336 points for Los Angeles from 2001-08 and became the face of the long-suffering franchise.
But the two-time All-Star forward left on sour terms once coach Mike Dunleavy said Brand backed out of a verbal agreement to return to the Clippers and then never offered an explanation why.
"If he called me up and said, 'Coach, I know I told you I was coming back, but I think a situation came up that's better for my family, I'm going to move on,' then, hey, sorry to hear it, but I wish you the best and good luck," Dunleavy said before the game.
Brand shook Dunleavy's hand and gave his former coach a quick embrace before the game.
Brand struggled most of the game from the floor, missing a couple of open looks late in the fourth that could have sliced Philadelphia's deficit.
Then he made up for it in a big way.
Thaddeus Young scored 17 points and Iguodala had 14 points and 12 rebounds for the Sixers.
Al Thornton scored 22 points for the Clippers, Baron Davis had 18 and Chris Kaman added 17.
Davis signed with the Clippers with the idea that he would play with Brand. Once Brand left for Philly, their relationship fizzled and Davis said this week he had nothing to say about Brand.
Davis sparked the Clippers in the third when he sank a 3, then blocked Iguodala's shot on the other end. The Clippers got the ball back and Eric Gordon made two free throws to help the Clippers take a 72-68 lead into the fourth.
The Sixers were sloppy in the fourth and the Clippers pounced. Thornton scored off a Sixers turnover at midcourt and Kaman followed with a three-point play to open an 83-75 lead.
Davis nailed a turnaround jumper for an 88-84 lead with 1:45 lead, but that was it for the Clippers.
The Clippers dropped to 2-10, one huge reason why Dunleavy said it was time to shake up the roster before the season slipped away.
Randolph, the 19th overall pick in the 2001 draft, led the Knicks with 20.5 points and 12.5 rebounds. He has career averages of 16.4 points and 8.2 rebounds over seven seasons and fills the void in the post the Clippers have missed since Brand left. Notes: Dunleavy was whistled for a technical in the third. ... Mobley averaged 13.7 points for the Clippers. Thomas, who signed with the Clippers in 2006, averaged 9.5 points. He played with the Knicks for parts of two seasons. Collins, a former Temple Owls standout, averaged 2.2 points and 1.7 assists in nine games.