In a stellar performance, James achieved a triple-double with 16 points, 11 assists, and 10 rebounds, leading the Lakers to break a three-game losing streak.
Seven players from the visiting Lakers racked up double figures, including Dalton Knecht with 20 points and Anthony Davis with 19.
French sensation Victor Wembanyama top scored for the Spurs with 20 points but could not stop his side's four-game winning streak coming to an end.
Elsewhere, Eastern Conference leaders the Cleveland Cavaliers suffered their first home defeat of the season and only their second loss of the campaign as they were beaten 135-124 by the Atlanta Hawks.
Trae Young recorded 20 points and a career-high 22 assists for the Hawks, while team-mate De'Andre Hunter scored 26 points.
"They are a really good team who have been playing well all year and I feel we have been a little inconsistent but the times that we have played well, we've played really well," said Young.
James Harden scored 43 points for the Los Angeles Clippers in their 121-96 win at the Washington Wizards.
It was Harden's highest points tally since March 2021 and came against a Wizards side who have lost 13 games in a row.
The Golden State Warriors were without the injured Stephen Curry and went down to a 105-101 home defeat against Western Conference leaders the Oklahoma City Thunder.
Shai Gilgeous-Alexander scored 35 points for the Thunder, while the Warriors suffered a third defeat in a row.
In Salt Lake City, Nikola Jokic contributed 30 points, 10 rebounds and seven assists to help the Denver Nuggets to a 122-103 victory against the Utah Jazz.
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