Sharp-shooting forward Durant scored a season-high 42 points and guard Russell Westbrook weighed in with 27 and 10 assists as the Thunder drew level with the Los Angeles Clippers at the top of the Western Conference.
Bench player Kevin Martin added 15 points on six-of-12 shooting and Oklahoma outshot Los Angeles by 51 percent to 40 from the field at a sell-out Staples Center while improving their record this season to 28-8.
"He's a special player," Martin said about Durant, the three-time reigning NBA scoring champion. "He's the heart of our team and we just like to follow his lead.
"He brought a lot of intensity and you see your superstar bring intensity like that, everybody else better bring it also."
Kobe Bryant led the way with 28 points for the Lakers, who slipped to 15-21 after playing their third consecutive game without injured big men Dwight Howard and Pau Gasol.
Howard, a three-time defensive player of the year, is out after re-aggravating a right shoulder injury while fellow All-Star Gasol is sidelined due to concussion.
"We have to put things in proper perspective," Thunder head coach Scott Brooks said after his team had out-rebounded the Lakers 53-46.
"They have some of their best players not playing tonight and they're short-handed. They're going to be a different team once they get everybody back.
"But we played well. Kevin had a hot hand and they missed some shots. When we defend and rebound, we're a pretty good team on the offensive end."
With Durant swiftly setting the tone, Oklahoma raced ahead 25-14, but Los Angeles closed the opening quarter on an unanswered 11-point run to tie the score at 25-25.
The Lakers twice took narrow leads before the Thunder relentlessly seized control and, with Durant and Martin each burying two three-pointers, stormed ahead 64-48 by halftime.
Durant continued to put on a show in the third quarter, draining a mix of three-pointers, jump shots and one extravagant slum dunk as Oklahoma stretched their lead to 93-73.
Though Durant slowed in the final quarter, Westbrook caught fire and added a further 10 points to keep the Lakers at bay.
"We played hard the whole game, they were just better," said Lakers head coach Mike D'Antoni. "Kevin Durant was just unstoppable. They were just longer, faster, better team-wise and we crumbled away. Second quarter really hurt us."
The Lakers lost six straight games for the first time since March 2007 and will aim to return to winnings ways when they host the struggling Cleveland Cavaliers (9-29) on Sunday.
"We put ourselves in this ditch and we are the only ones that can get us out," said D'Antoni. "Hopefully we can get some guys back and start our season on Sunday."
Antawn Jamison added 19 points and 10 rebounds for the Lakers off the bench but veteran point guard Steve Nash had a quiet game with seven points and seven assists in 30 minutes.
"I think we showed some fight but we were just a little over-matched," Nash said. "They're bigger than us at almost every position. Kevin got hot and we couldn't contain him in the second quarter."
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