Tim Duncan added 24 points and 11 rebounds for the Spurs who moved into sole possession of seventh in the Western Conference.
"Unbelievable victory," Ginobili told reporters after making 10 of 22 shots. "I would say like two months ago it wasn't even in our wildest dreams to win a game by (19) against the Lakers."
Pau Gasol scored 32 points and Kobe Bryant added 22 for the Lakers (55-22) who are trying to wrap up the top seed in the West but suffered their third defeat in their last four games.
The defeat allowed the Cleveland Cavaliers to clinch the best record in the league and ensure home court advantage throughout the NBA Finals.
The Spurs (47-29) took an eight-point lead at halftime before a 13-1 run in the fourth broke the game open.
The Lakers pulled within two points with 8:38 left in the fourth but Ginobili closed the game with 15 points in the final nine minutes to help San Antonio put the game away.
The Argentine, who has picked up the scoring load in the absence of All Star Tony Parker, also scored 43 points in a win against the Orlando Magic on Friday.
San Antonio, who lost point guard George Hill to a sprained ankle in the second quarter, have won five of its last six.
Los Angeles was coming off an impressive 106-92 win over the Utah Jazz on Friday but fell flat on Sunday.
Gasol's point total was a season-high but Bryant struggled for the second successive game. He finished 8-for-24 from the field and has made just 13 of his last 47 shots.
"We want to end these last five games on a good note," Gasol said. "We have to feel good about ourselves going into the playoffs. That's important, so obviously we want consistency."
(Editing by Greg Stutchbury)