Spurs point guard Tony Parker scored 25 points on 11-of-16 shooting while forward Kawhi Leonard chipped in with a double-double of 22 points and 10 rebounds, as did Tim Duncan, who had 12 points, 16 rebounds and six assists.
The Lakers kept close with a 19-point effort in the first half from forward Xavier Henry, who finished with 24. Pau Gasolalso scored 24, to go along with 10 rebounds and six assists.
The Lakers shot 42.9% from the field and 34.6% from three-point range while turning the ball over a reasonable 12 times, despite playing with just one true point guard in Kendall Marshall.
Marshall finished with 10 points but only three assists. The Lakers had just 19 assists on 39 baskets.
The Spurs finished with an efficient night, making 52.6% of their shots from the field and 44.4% from three-point range while also committing 12 turnovers.
The Lakers are 22-45 after losing their third in a row. They'll host the Washington Wizards (35-32) on Friday night.
San Antonio (51-16) will travel to Sacramento to play the Kings (24-44), also on Friday.
The Spurs gained control in the third quarter, but were not able to put away the Lakers.
The Spurs are shooting 50% from the field and 45% from three-point range through three quarters. Point guard Tony Parker leads San Antonio with 21 points.
The Lakers have made 48.6% of their shots from the field and 36.8% from long range to stay within five. Pau Gasol leads the Lakers with 21 points. He has eight rebounds and five assists.
Xavier Henry had 19 points in the first half but didn't score in the third.
The Lakers outscored the Spurs, 13-5, early in the second quarter, to take a 42-40 lead.
Swingman Xavier Henry scored 11 points in the quarter and leads all scorers with 19 at halftime.
Point guard Tony Parker, who has 13 points, pushed the Spurs back on top by nine in the second quarter. Forward Ryan Kelly's dunk with less than a second on the clock got the Lakers back to within a single point at the half.