In the first match-up between the teams since World Peace struck James Harden with an elbow on April 22 to draw a seven-game suspension, the Thunder hit back to take a 1-0 series lead.
Russell Westbrook had 27 points, nine assists and seven rebounds in limited playing time, Kevin Durant added 25 as a rested Oklahoma City team ran circles around the visitors.
"I just tried to come out aggressive, we hadn't played in a while and I had some good legs underneath me," Westbrook said.
The Thunder swept their first-round series and had more than a week off while the Lakers just wrapped up a tough seven-game series two days ago.
Kobe Bryant and Andrew Bynum both had 20 points, but the Lakers fell behind by 15 at halftime and the deficit ballooned to 30 in the third as the visitors struggled to cope with Oklahoma City's foot speed and athleticism.
A hostile home crowd booed World Peace throughout the night but Harden said he did not let the elbowing incident interfere with his focus.
"(I) put that stuff behind me and (went) out there to make plays for my team," said Harden, who had 17 points to World Peace's 12.
In the Eastern Conference, Philadelphia avoided a repeat of their Game One flop and earned an 82-81 road triumph over Boston, outdueling the Celtics late to tie their second round play-off series.
After blowing a 10-point advantage in the fourth quarter to lose the series opener on Saturday, the youthful 76ers again saw a late lead disappear but this time they refused to buckle and tied the best-of-seven series 1-1.
Jrue Holiday scored a team-high 18 points while Evan Turner made a go-ahead scoop shot with 40 seconds left and added two key free throws during a rugged struggle that heated up in the final quarter.
Ray Allen had 17 and Kevin Garnett added 15 and 12 rebounds and made a three-pointer as time expired to shave the final deficit.
Game Three is on Wednesday in Philadelphia.