In the highly anticipated first showdown of the season between Doncic and Wembanyama, Slovenian star Doncic delivered a masterful 35 points, nine rebounds and 13 assists.
He added five steals and two blocked shots as the Lakers prevailed in a chaotic finish at Crypto.com Arena, improving to 7-2 as they wait for injured superstar LeBron James to make his season debut.
Wembanyama led the Spurs with 19 points, eight rebounds and three assists.
Stephon Castle and Jeremy Sochan scored 16 points apiece as seven San Antonio players registered double figures -- but their balanced attack wasn't enough.
Wembanyama was in foul trouble much of the game and fouled out with 1:40 remaining and the Spurs trailing 113-112.
The Lakers were clinging to a 118-116 lead with 1.2 seconds remaining when their botched inbounds play gave the Spurs the ball, but San Antonio couldn't capitalise.
"They have an amazing team. They only lost one (other) game, so to come back, being with (Austin Reaves) and LeBron out, it's unbelievable," Doncic said.
In Portland, the Trail Blazers erased a 22-point deficit to stun the Thunder 121-119, ending Oklahoma City's 8-0 winning streak to start the season.
Deni Avdija scored 26 points with 10 rebounds and nine assists and Jrue Holiday added 22 points for the Trail Blazers, who took their first lead of the game, 97-96, on a Holiday jump shot with 6:44 remaining.
The teams would swap the lead four more times before the Blazers managed to pull away.
NBA Most Valuable Player Shai Gilgeous-Alexander made a pair of free throws to pull the Thunder within one with 7.1 seconds left, but Holiday followed with two free throws that proved enough.
Gilgeous-Alexander finished with 35 points, nine rebounds and four assists and Aaron Wiggins added 27 points for OKC, who led by 22 in an explosive first quarter and by 14 late in the third.
Nets get first win
The Brooklyn Nets finally grabbed their first victory of the season, beating the injury-depleted Indiana Pacers 112-103.
Forward Michael Porter Jr., back after missing a game for personal reasons, scored 32 points and grabbed 11 rebounds to lead the five Nets players who scored double figures.
Nic Claxton added 18 points, 10 rebounds, six assists, three steals and two blocked shots for Brooklyn, who scored 23 points off 18 Pacers turnovers.
Pascal Siakam scored 23 points and handed out 10 assists for Indiana, who put up 41 points in the second quarter and led 59-54 at halftime in a tight game that featured a dozen lead changes.
"I'm really proud of the whole group and being part of the win, it's very special," Nets coach Jordi Fernandez said.
"We look like a competitive group, we look like a selfless group and we look like a connected group and that's how we see our future in the short term and the long term.
"Winning starts now, and when you go out there and fight like this, that's what we care for now and the future."
The New York Knicks scored 83 points in the second half to surge to a 137-114 victory over Minnesota at Madison Square Garden, spoiling the return of Timberwolves star Anthony Edwards after a four-game absence with a strained right hamstring.
Nikola Jokic's latest triple-double -- 33 points, 15 rebounds and 16 assists -- powered the Denver Nuggets to a 122-112 victory over the Miami Heat.
Norman Powell scored 23 points to lead the Heat, who saw star centre Bam Adebayo exit with a foot injury in the first half.
In Cleveland, Donovan Mitchell scored 46 points to lead the Cavaliers to a 132-121 victory over the Philadelphia 76ers.