The host Thunder improved to an NBA-best 17-1 and stretched their win streak to nine games by defeating the Trail Blazers, who kept them from a perfect start with a 121-119 upset at Portland on November 5.
Gilgeous-Alexander made 13-of-18 shots from the floor, two-of-three from three-point range, and all nine of his free throws while adding seven assists, five rebounds and two steals.
"He's a killer and we know that," teammate Ajay Mitchell said of Gilgeous-Alexander. "Seeing him in that zone is always a pleasure to watch."
Oklahoma City became only the fifth NBA team in the past 30 years to begin a campaign 17-1, joining Cleveland last season, Golden State in 2015, Dallas in 2002 and Chicago in 1996.
Mitchell had 20 points off the bench on eight-of-eight shooting, two-of-two from three-point range.
"Glad we got the win. Glad I got a good game. Happy about it," Mitchell said. "(The key was) just being prepared and being ready for 48 minutes.
"We started off well and we just kept going. That's what we've got to keep doing every single game."
Isaiah Hartenstein grabbed 15 rebounds for the Thunder, who improved to 7-0 at home.
The Los Angeles Lakers, led by 33 points and 11 rebounds from Luka Doncic, stretched their win streak to four games with a 108-106 victory at Utah.
LeBron James, in his first road game of the season after being sidelined by sciatica, scored 17 points in 34 minutes on eight-of-18 shooting but missed all four three-point attempts. He also had eight assists and six rebounds.
Austin Reaves added 22 points and 10 rebounds for the Lakers, who improved to 12-4.
Keyonte George, who led Utah with 27 points, missed a three-point in the final seconds to seal the Lakers' triumph.
At Phoenix, Dillon Brooks scored 25 points and Devin Booker added 24 to lead the host Suns over San Antonio 111-102.
The Spurs, playing without injured French star Victor Wembanyama, fell to 11-5 with a three-game win streak snapped.
Cleveland's Donovan Mitchell unleashed a 37-point performance with eight rebounds and six assists to spark the Cavaliers over the visiting Los Angeles Clippers 120-105.
Ivica Zubac led the Clippers with 33 points and 18 rebounds.
Jaylen Brown scored 35 points to lead the Boston Celtics over visiting Orlando 138-129. Anfernee Simons added 23 off the bench for Boston while Magic reserve Jeff Hoard had 30 points.
Host Atlanta had 28 points, 11 assists and eight rebounds from Jalen Johnson and Nickeil Alexander-Walker added 23 to lift the Hawks over Charlotte 113-110.
Alexander-Walker's layup lifted Atlanta ahead 111-110 with 1:42 remaining and he added two late free throws to seal Charlotte's fate, the Hornets going scoreless over the final three minutes as Atlanta ended the game on a 6-0 run over 2:14.
Raptors win 11 of 12
At Toronto, Scottie Barnes led eight double-figure scorers with 17 points to power the host Raptors over Brooklyn 119-109.
The Raptors (12-5), second in the Eastern Conference, stretched their win streak to seven games with an 11th victory in 12 contests.
Miami's Norman Powell scored 32 points and Kel'el Ware added 20 points and 16 rebounds to spark the Heat's 127-117 home victory over Philadelphia. Tyrese Maxey scored 27 points in a losing cause as Miami (11-6) saw their win streak hit four games.
Kevin Durant will miss Houston's next two games while tending to a family matter, ESPN and The Athletic reported. He won't play in road games against two of his former clubs, Phoenix on Monday and Golden State on Wednesday.
Denver's Aaron Gordon will be sidelined by a hamstring strain for four to six weeks, the Nuggets announced Sunday.