The victory was the Thunder's seventh in a row, and their 16th win of the season, while the Lakers are struggling at 9-11.
After trailing by a point after the first quarter, the Thunder (16-4) exploded in the second with 41 to open up a 14-point lead at the half, a gap the Lakers could not reel in.
"That was a solid win, we had some very good stretches but then in the second half we had some not so good stretches. We relaxed some on defense in the second half," Thunder coach Scott Brooks said.
Westbrook had a huge first half, scoring 27 of his 33 points to help the Thunder open up the big gap.
The battle of the scoring big guns went to Thunder forward Kevin Durant with 36 points and nine rebounds, while Lakers guard Kobe Bryant finished with 35 points.
"It wasn't us, Westbrook just went crazy on us and they're a great shooting basketball team that had a hot quarter," Lakers coach Mike D'Antoni told reporters.
"When he does that, when he has that vertical and when he stops on a dime, you just have to tip your hat a little bit."
The teams met in the Western Conference semi-finals last season with the Thunder winning in five games before eventually losing to the Miami Heat in the NBA Finals.
While the Thunder had the upper hand on Friday, the Lakers will undoubtedly improve with the return of Steve Nash, Steve Blake and Pau Gasol.
"They set a bar," D'Antoni added. "We know where we got to go and I'm encouraged by some of the stuff we're doing. I thought Dwight (Howard) and Kobe had great games and it's important they play well together."
Howard contributed 23 points and 18 rebounds.
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