Philadelphia, PA – Lou Williams scored 14 of his 24 points in 90, at Wells Fargo Center.
Jrue Holiday added 13 points and six assists for the Sixers, who had dropped their last four games against the Lakers. Andre Iguodala finished with 12 points in Philadelphia's sixth win in its last seven games.
Kobe Bryant scored 24 points on 4-of-6 shooting from three-point range in the first half. He struggled in the second half, ending with 28 points, but still surpassed former teammate Shaquille O'Neal for fifth place on the NBA's all- time scoring list.
"It's a huge honor," Bryant said of his latest accomplishment. "I've been very fortunate."
Andrew Bynum poured in 20 points and pulled down a game-best 20 rebounds as LA dropped its second straight contest.
Philadelphia held a slim 70-69 advantage entering the fourth quarter, but scored just nine points over the first seven minutes of the frame as the Lakers jumped out to an 86-79 lead with 4 1/2 minutes left in the game.
But then Williams turned it on, scoring 10 points in a game-changing 14-2 run by the Sixers to put them ahead, 93-88.
Bryant then brought the Lakers within three on a fadeaway jumper with just over a minute left and Los Angeles had a chance to get within one after Williams missed a three-point attempt on the other end.
However, Bryant's off-balance shot rimmed out and Pau Gasol's putback attempt also missed, leading to Williams' game-sealing foul shots.
"That was an amazing win for us. I didn't know how we were going to battle through their size," Philadelphia head coach Doug Collins said. "Lou [Williams] got hot at the right time for us,"
After the Sixers scored the first points of the game on a Holiday jumper, Los Angeles reeled off nine straight points to jump out to a 9-2 advantage as Philadelphia went 1-for-7 from the floor.
Lavoy Allen's short hook shot snapped the Lakers' run and sparked a 6-0 swing by the Sixers to bring them within one.
The remainder of the first quarter saw four ties and the lead change hands twice before Bynum's putback gave the Lakers a 24-21 lead entering the second quarter.
It remained a tight game through a back-and-forth opening six minutes of the second, but a 9-2 spurt by the Lakers gave them their largest lead of the game so far, 45-38.
Philadelphia, though, responded with three-pointers by Iguodala and Jodie Meeks around Gasol making the back end of two free throws to close the gap to four and Los Angeles held a 50-46 lead at the break.
The Lakers took a 57-52 advantage four minutes into the third quarter as the teams traded buckets before the Sixers ripped off a 13-4 run for a 65-61 lead late in the third.
Los Angeles battled back to take a one-point lead in the final minute of the quarter, but Thaddeus Young's jumper gave Philadelphia a 70-69 edge entering the final stanza.
Bryant now has 28,601 career points. Wilt Chamberlain currently sits comfortably ahead in fourth place with 31,419 points...Sixers forward Elton Brand missed his second straight game with a sprained right thumb...Los Angeles Lakers head coach Mike Brown was not on the sidelines after being suspended one game and fined $25,000 following his ejection from the February 4 game against Utah...Philadelphia improved to 13-3 at home this season, while the Lakers fell to 3-9 on the road.