George, a native of nearby Palmdale, Calif., who is rumored to be interested in signing with the Lakers as a free agent next offseason, tied for the team high with 24 points.
Terrance Ferguson poured in 24 points with six 3-pointers in his first career NBA start in place of Andre Roberson, who was sidelined due to a knee injury.
Reigning NBA MVP Russell Westbrook, who played in college at UCLA, had 20 points, 12 assists and six rebounds. Carmelo Anthony added 21 for the Thunder, all in the first half.
Oklahoma City (21-17) shot a blistering 60.2 percent from the field to snap a two-game skid that followed a six-game winning streak.
Kyle Kuzma scored 18 points to pace the Lakers. Kentavious Caldwell-Pope had 12, Jordan Clarkson 11 and Corey Brewer 10 as Los Angeles (11-26) lost its eighth straight.
After missing eight games because of an ankle injury, Lakers center Brook Lopez returned to score 10 points and grab five rebounds in 16 minutes.
The Lakers were again without No. 2 overall pick and starting point guard Lonzo Ball, who missed his seventh consecutive game due to a sprained left shoulder.
Ball has been cleared to practice and will do so Thursday with the intent of returning for the Friday home game against the Charlotte Hornets.
Both Lopez and Ball were officially questionable for the Wednesday game.
The Thunder led 63-44 at halftime after pulling away in the second quarter, outscoring the Lakers 37-18 in the period.
Lopez's 3-pointer with 8:38 to play in the second put Los Angeles up 34-32. The game was tied at 35 at the 8:09 mark before Oklahoma City effectively put the contest away with an 18-4 surge. The Thunder ended the half on a 28-9 run.
That trend continued in the third as the Thunder posted a 33-26 advantage and coasted to victory in the fourth.
Los Angeles scored the first 10 points of the game but was outscored 26-16 after that as Oklahoma City pulled into a tie after one quarter.
The Thunder stay in Los Angeles to face the Clippers on Thursday.
--Field Level Media
Oklahoma City | L.A. Lakers | |
Terrance Ferguson 24 | Scoring | Kyle Kuzma 18 |
Russell Westbrook 12 | Assists | Tyler Ennis 6 |
Josh Huestis 9 | Rebounds | Larry Nance Jr. 7 |
Paul George 3 | Free Throws Made | Julius Randle 3 |
Terrance Ferguson 3 | Steals | Jordan Clarkson 1 |
Steven Adams 3 | Blocks | Kyle Kuzma 2 |
Team | Points | FG% | 3PM-3PA | FTM-FTA | Assists | Rebounds | Blocks | Steals | Turnovers |
Oklahoma City | 133 | 60.2 | 14-30 | 7-9 | 36 | 44 | 5 | 12 | 9 |
L.A. Lakers | 96 | 41.3 | 11-33 | 9-15 | 24 | 45 | 4 | 5 | 17 |