Isaiah Joe added 21 points for the Thunder, who improved to a league-best 12-1.
Oklahoma City crushed one of its Western Conference rivals in Game 2. They beat the Golden State Warriors 126-102 on Tuesday night.
Los Angeles guard Luka Doncic scored 19 points on 7-of-20 shooting after averaging 37.1 points entering the game.
Oklahoma City's Lou Dort, the guard who usually protects Doncic, was out with a right upper trapezius strain, but the Thunder got the job done anyway.
Austin Reaves, who averaged 30.3 points, scored 13 points on 4-for-12 shooting for the Lakers. Los Angeles has scored at least 116 points in every game this season, but hasn't gotten close to that after shooting 40.3 percent from the field.
The Lakers played without LeBron James again, although he practiced Wednesday for the first time this season. Earlier in the day in California, he received several representatives from the team's G League affiliate.
Los Angeles could use another star against Oklahoma City. The Thunder led 30-18 at the end of the first quarter, then held the Lakers without a field goal for nearly eight minutes before starting the second. Los Angeles missed its first 11 shots of the quarter, and Oklahoma City extended its lead to 70-38 at the break.
In the final seconds of the third quarter, Gilgeous-Alexander drove to the rim, then made an behind-the-back pass to Joe, who hit a 3-pointer as time expired to give Oklahoma City a 100-64 lead.
Lakers: Visit the New Orleans Pelicans on Friday.
Thunder: Visit the Charlotte Hornets on Saturday.
