Bryant scored 22 points while playing only three quarters.
He was not needed in the fourth after the Lakers turned a six-point halftime lead into a 15-point spread in the third quarter. The margin eventually went to 21 in the fourth.
"We played a stellar game and our bench was the difference breaking the game and holding the lead," Lakers coach Phil Jackson told reporters.
"They (Spurs) just didn't shoot the ball well (in the second half) and we were able to jump out a little bit on them."
The victory avenged a one-point loss by the conference-leading Lakers at No. 2 San Antonio on January 14 and snapped a four-game Spurs winning streak.
This time, Los Angeles got 17 points from reserve Trevor Ariza plus 16 points and some timely passes from Pau Gasol in winning for the 23rd time in 26 home games.
Center Andrew Bynum contributed 15 points and 11 rebounds and Jordan Farmar, who had not played since December 19 because of torn knee cartilage that required surgery, added 14 points.
"We miss (Farmar) a lot," Bryant told reporters. "He makes our second unit go. Now that he is back everybody falls into their natural positions and we are back clicking on all cylinders."
Lakers coach Jackson said Bynum's play also was important.
"He doesn't show a lot of emotion," he said. "But, you know, he does get to work. And he's a guy that's learning how to be a pro."
Tony Parker led the Spurs with 19 points. Tim Duncan was the only other San Antonio player in double figures with 15 points and eight rebounds. Both rested much of the fourth quarter, as did most of the Los Angeles starters.
San Antonio's Manu Ginobili, who came into the game averaging 15.1 points, finished with nine points and eight rebounds.
"We just try to make his life a little difficult," Bryant said.
Spurs coach Greg Popovich said he thought the game got away from his team in the first two minutes of the third quarter.
"We let go two quick threes with bad rotations and never caught up after that," Popovich said. "The game was over at that point."
