CJ McCollum added 28 points for the Blazers, who have won three of their last four games after a six-game losing streak.
Kobe Bryant scored 21 points in the Lakers' seventh straight road loss.
It was Portland's seventh straight victory over the Lakers.
Jordan Clarkson added 19 points for the Lakers.
The Blazers led by as many as 17 points in the first half but the Lakers closed within five in the third quarter.
McCollum's jumper put Portland up 90-78 early in the fourth and the Blazers kept the Lakers from making up much ground down the stretch. His 3-pointer with 2:27 left gave the Blazers a 104-93 lead.
The Blazers welcomed back Meyers Leonard, who missed seven games with a dislocated left shoulder. The 7-foot-1 forward was averaging 12.3 points and 5.8 rebounds in the four games before his injury.
Leonard came off the bench and finished with seven points and six rebounds in 22 minutes.
The Lakers were playing the first of a back-to-back. They host the Pacers on Sunday before embarking on an eight-game road trip.
Bryant, playing in possibly his last season, was averaging 15.2 points going into the game, shooting just 31.1 percent from the field and 19.5 percent from 3-point range. He was 7 of 20 from the field Saturday and 1 of 5 on 3-point attempts.
Coach Byron Scott suggested in recent days that he may tinker with his starting lineup. He stayed with his regulars against the Blazers, and Los Angeles fell behind 27-14 in the opening quarter after Lillard hit a 3-pointer.
Leonard hit a 3-pointer to put the Blazers up 49-34, but the Lakers closed the gap with a 7-0 run capped by Julius Randle's mid-range jumper and free throw that made it 49-42.
Bryant crashed to the floor after a layup with about 2 minutes to go in the first half and appeared to clutch his back when he got up, but he stayed in the game following a timeout.
He played 34 minutes, making it unlikely he'll play against the Pacers on Sunday.
The Blazers led 60-46 at the break following McCollum's 3-pointer. McCollum led all players with 19 points.
Los Angeles narrowed the margin again, pulling within 70-65 midway through the third quarter after D'Angelo Russell's free throws. Lillard's 3-pointer and a free throw stretched the lead back to 80-70.
Lakers: Los Angeles was playing without guard Lou Williams because of personal reasons. He is likely to miss Sunday's game, too, Scott said before the game. ... The Lakers are 0-8 against the Western Conference.
Trail Blazers: Lillard had scored at least 30 points in four of his previous six games against the Lakers. ... Lillard has 13 games with 20 or more points and five or more assists. ... Former "Saturday Night Live" cast member Tim Meadows was in the crowd.
Lakers: Host Indiana on Sunday.
Trail Blazers: Visit the Clippers on Monday.