Westbrook, who earlier sparked a 13-0 run that pulled the Thunder out of a third-quarter deficit, hit the decisive basket with a driving layup that made it 86-85 with 2:19 to play and Oklahoma City stopped Minnesota on its next six possessions to hang on for the win.
"We're going to have to be scrappy to win games," said Westbrook, the No. 4 overall pick in this year's draft and the first building block in the franchise's defensive overhaul.
Westbrook was hardly the flashy pick so early in the draft, overshadowed by Memphis' Derrick Rose and Kansas State's Michael Beasley - the first two players taken. Even former teammate Kevin Love, who plays for Minnesota, got more headlines than Westbrook in their time at UCLA.
But Westbrook might be just what the Thunder need to improve on a defense that gave up the fourth-most points in the NBA last season as the Seattle SuperSonics. After giving up 106.3 points last season, none of Oklahoma City's first three opponents have even hit triple digits.
The improvement was clear down the stretch, as Minnesota scored only two points in the final 5 minutes - on Al Jefferson's putback of Randy Foye's missed 3-pointer that gave the Timberwolves an 85-84 lead with 2:43 left.
Westbrook answered with his layup at the other end, and Ryan Gomes, Jefferson and Foye all missed chances to give the Timberwolves the lead before Nick Collison's left-handed hook shot with 16.4 seconds left made it a three-point game.
After a pair of missed free throws by Jeff Green gave Minnesota one last chance, Gomes missed a potential tying 3-pointer from the left side to close the game. Officials huddled by a courtside monitor to see if there was a foul before the final buzzer, and cheerleaders ran onto the court to start the celebration anyway.
It turned out the Thunder's first win with their new identity was safe after all.
"Any win feels good, honestly," Oklahoma City coach P.J. Carlesimo said. "It's very good to get a win in this building. It's very good to get a win the way we got it."
Kevin Durant led the Thunder with 18 points despite a 7-for-21 shooting night. Green added 13 points, Chris Wilcox scored 12 off the bench and Collison had 10 points and 10 rebounds for his first double-double.
Minnesota's Al Jefferson had 24 points and 13 rebounds for his third straight double-double to start the season, but the Thunder clamped down late on him. Craig Smith added 13 points, Gomes scored 12 and Mike Miller had 10.
"It's a game we're supposed to have won," Jefferson said. "We gave up 25 points second-chance. That's why it hurts so bad. ... No disrespect to the Thunder, but it was just a game we had in the bag and we should have won."
The Thunder got off to slow starts in each of the first three quarters, going 3-for-13 from the field to open the game and then giving up a 9-0 run to start the second quarter and a 7-0 spurt right after halftime.
Each time, Oklahoma City came back - and Westbrook finally got his team over the top.
He had steals on back-to-back possessions late in the third quarter, turning the first into a three-point play that sparked a 13-0 run for the Thunder. He also finished off the surge with a driving finger roll for a 76-73 Oklahoma City lead early in the fourth quarter.
With Westbrook playing so well, Carlesimo left him in down the stretch alongside fellow point guard Earl Watson instead of going with his initial plan to go with the veteran Wilcox and a bigger lineup.
"I just thought we needed Earl to settle us down I think we did not want to take Russell out of the game," Carlesimo said. "I was kind of boxed in."
It turned out to be exactly what the Thunder needed.
Notes: Collison had seven of Oklahoma City's 19 offensive rebounds. The Thunder had 25 second-chance points to 11 for Minnesota. ... The Timberwolves were 16-for-16 from the free-throw line. After winning their opener despite an 11-for-22 performance against Sacramento, the Wolves have lost their last two games while making 38 of 40 at the foul line. ... Foye was 0-for-10 and had his only two points on free throws.