With "Beat L.A.!" echoing through a second straight sellout crowd, Williams hit the tying jumper, then followed with the 3 for a 91-88 lead. He hit another floater to make it 93-88, part of a fantastic fourth that saw him hold off Bryant and help the Sixers improve to 13-3 at home.
Bryant scored 24 of his 28 points in the first half. He passed former teammate Shaquille O'Neal and moved into fifth place on the NBA's career scoring list. Bryant got 24 points in a hurry to pass O'Neal, but stumbled down the stretch and missed nine of his 10 shots in the fourth.
Andrew Bynum had 20 points and 20 rebounds for the Lakers. Pau Gasol had 16 points and 11 rebounds.
The Sixers went 3-1 last week against a fierce lineup of Orlando, Chicago, Miami (the loss) and Atlanta. It's more of the same this week: San Antonio is here Wednesday and the Los Angeles Clippers on Friday.
The Sixers have proven they can handle the rugged schedule.
They committed only four turnovers, a minuscule number that was enough to make up for getting pounded on the boards. Led by Bynum and Gasol, the Lakers outrebounded Philadelphia 55-30.
Williams, one of the top sixth men in the NBA, has never been afraid to take the clutch shot. While the Sixers have soared in the East this season with a team-oriented approach, Williams is the one the Sixers want with the ball and the game on the line.
Lakers coach Mike Brown served a one-game suspension for making contact with a game official and failure to leave the court in a timely manner following his ejection in Saturday's game. He also was fined $25,000. John Keuster filled in for Brown.
Bryant started like a shooter determined to score 50.
His first bucket saw the ball take a few whirls around the rim before plopping through the net. Bryant buried a 3, then backed down Evan Turner and used a soft touch off a spin move for seven quick points.
He stared down Andre Iguodala for a 3. Bryant nailed two more 3-pointers - each one drawing more boos than the last - and had 22 points in the second quarter.
For the record setter, Bryant cut toward the top of the 3-point arc, took as a fast feed from Matt Barnes and hit the 23-footer.
Originally called a 3, Bryant had his foot on the line. Three points or two, it was enough to pass O'Neal.
Bryant went 8 for 14 from the floor and made 4 of 6 3s in the first half to help the Lakers lead 50-46 at the break.
He went into hibernation until an up-and-under bucket late in the third pulled the Lakers to 63-61.
O'Neal and Bryant often clashed, even while leading the Lakers to NBA championships in 2000, 2001 and 2002. O'Neal won an NBA championship with Miami in 2006 to briefly edge Bryant in total championships. Under coach Phil Jackson, Bryant won consecutive championships in 2009 and 2010, and had long ago cemented his spot as one of the NBA's all-time greats.
Kobe already had more championship rings than Shaq. He has more points, too.
The Sixers failed to acknowledge the special achievement.
Bryant, who spent eight years of his childhood in Italy before returning to the area to attend high school, had already been the youngest player in NBA history to reach 28,000 points.
Bryant led Lower Merion to a state championship in 1996 and still makes visits and donations to the school.
The relationship between Philly fans and Bryant has been strained since the 2001 NBA finals against the Sixers, when he proclaimed he was "coming to Philly to cut their hearts out." That began an unforgiving attitude from Sixers fanatics that continues to this day.
When commissioner David Stern presented Bryant with the All-Star game MVP trophy in 2002 in Philadelphia, the boos were long and loud, and he later admitted he was hurt.
He now feeds off Philadelphia's official sound and delights in upsetting the home crowd.
It just wasn't enough to upset the 76ers.
Notes: 76ers F Elton Brand sat out with a sprained right thumb. Lavoy Allen got the start. ... Kareem Abdul-Jabbar, Karl Malone, Michael Jordan and Wilt Chamberlain are ahead of Bryant on the scoring list. ... The Sixers 14 rebounds in the first half was a season low.