Kobe Bryant had 27 points and 10 rebounds while Pau Gasol added 20 points and 14 rebounds for the Lakers (27-11), who held New York to its second lowest point total of the season.
The Knicks, who entered the game averaging a league-best 108.1 points per game, shot just 36 percent from the field as they had their three-game win streak snapped.
"We played good team defense and took them out of their comfort zones," Lakers forward Lamar Odom told reporters after finishing with 13 points and 18 rebounds.
"We just tried to play hard tonight and play a tough game. We were able to do that and get the win." Los Angeles led by six points at halftime but stretched its lead to 16 in the third quarter, where Bryant began things with consecutive three-pointers.
The Knicks trimmed the lead to eight early in the fourth but went long stretches without scoring in the final period where they tallied just 17 points and fell far behind.
Amare Stoudemire had 23 points and 10 rebounds, but made just 7 of 24 shots, and Wilson Chandler added 19 for New York (21-15).
The Knicks were playing the second of a four-game Western Conference road trip and had demolished Phoenix 121-96 on Friday.
New York has emerged as a threat this season after signing Stoudemire in the summer but they still have not beaten the Lakers since 2007.
Los Angeles dominated inside with a 61-42 rebounding advantage and controlled a physical and sometimes testy contest.
Lakers center Andrew Bynum scored 18 points before he was ejected with two quick technical fouls early in the fourth where he protested a foul call.
"I have no idea (why I was ejected). I guess he felt like I showed him up and he T'd me up," said Bynum, who is showing continued improvement since returning last month following knee surgery. "I'm getting back in a rhythm and feeling pretty good."
In Portland LeBron James had 44 points, 13 rebounds and six assists and Dwyane Wade added 34 points as the Miami Heat beat the Portland Trail Blazers 107-100 in overtime Sunday in the NBA.
James buried two deep 3-pointers and made two free throws in the extra period for the Heat (30-9), who have won 21 of their last 22 games after a slow start to the season.
Chris Bosh added 18 points and eight rebounds. The Big Three combined for all but 11 of Miami's points.
The victory was the Heat's 13th straight on the road.
Miami is now three road wins away from tying the NBA record held by the 1971-72 Los Angeles Lakers.
LaMarcus Aldridge had 31 points, 14 rebounds and seven assists for the Blazers.
In Denver, Carmelo Anthony scored just eight points and was booed by the home crowd as New Orleans beat the Nuggets in one of the worst performances of the superstar's career.
The loss put a sour finish on a day filled with speculation that Anthony's departure from Denver was close after 71/2 seasons. A person with knowledge of the discussions told The Associated Press on Sunday night the Nuggets were closing in on a deal that would send Anthony to New Jersey in a three-team trade.
Anthony had taken just five shots before the fourth quarter and finished 3 for 11 from the floor.
Chris Paul scored 20 points and David West had 19 to lead New Orleans.
In Toronto, Andrea Bargnani scored 30 points and DeMar DeRozan had 28 to help Toronto hold off lowly Sacramento.
Leandro Barbosa added 18 points - including 11 in the fourth quarter - for the Raptors, who had dropped 13 of their previous 17 games.
After DeMarcus Cousins scored on a dunk, a tip-in and a layup to bring the Kings to within one point with 1:06 remaining, Bargnani made a 3-pointer and Barbosa grabbed the rebound on a missed 3 at the other end to seal the victory.
Beno Udrih scored 25 points and Carl Landry had 22 for the Kings, who dropped their 10th straight road game.
In Los Angeles, Eric Gordon scored 25 points and Blake Griffin had 23 points and 12 rebounds to lead the Clippers over Golden State.
Baron Davis added 17 points and 11 assists for the Clippers, who won for the seventh time in 10 games after a 5-21 start to the season.
The rookie Griffin reached double figures in points and rebounds for a club-record 23rd consecutive game.
Dorell Wright scored 27 points for the Warriors, who had won six of nine. Monta Ellis, the NBA's third-leading scorer, managed just 13 points on 4 for 19 shooting.
In San Antonio, Manu Ginobili scored 14 of his 21 points in the second quarter as San Antonio rallied to beat Minnesota.
San Antonio won its 15th straight game over the Timberwolves - the league's longest current winning streak against an opponent.
George Hill's free throws with 3:24 in the fourth gave the Spurs a 94-86 lead, but they did not score again. Luke Ridnour's 3-pointer with 1:40 left cut the lead to 94-91, but he missed another 3-point shot to tie the game with 31 seconds remaining.
Kevin Love had 18 points and 17 rebounds and Ridnour added 16 points in Minnesota's fourth straight loss.
At Phoenix, Steve Nash had 20 points and 15 assists as the Suns handed undermanned Cleveland its 10th straight loss.
The loss was the 20th in 21 games for the Cavaliers, who also lost center Anderson Varejao for the season Sunday after an MRI showed the Brazilian had torn his ankle tendon.
Jared Dudley came off the bench to score 21 points and Vince Carter added 19 for Phoenix.
Rookie Manny Harris scored a season-high 27 points and J.J. Hickson had 23 points and 17 rebounds for Cleveland.
