Kobe Bryant had 22 points and Smush Parker scored 20 for the Lakers (28-19), who lost for the fourth consecutive time at Conseco Fieldhouse.
Jamaal Tinsley finished with 16 points, Darrell Armstrong and Danny Granger each had 14 and O'Neal grabbed nine rebounds for Indiana (25-21), which won for the fifth time in six games.
Trailing 70-61 late in the third quarter, the Pacers scored nine consecutive points to tie the score early in the fourth.
Minutes later, Armstrong and Tinsley hit consecutive 3s to spark the winning run. Granger's layup gave the Pacers an 89-76 lead with 1:30 left.
The Pacers jumped to an early double-digit lead behind O'Neal's 13 points. Mike Dunleavy's layup gave Indiana a 24-12 advantage with 3 minutes left in the first quarter.
The Lakers chipped away at the deficit in the second quarter, getting within 36-33 after Brian Cook's 3-pointer that capped a 7-0 run. The Pacers regained a 44-38 lead, but Bryant hit three free throws to end the first half.