Wells had 27 points, 10 rebounds and a crucial steal in the final minute and was one of five players in double figures as the Trail Blazers snapped a five-game losing streak against the Lakers, holding on for a 111-105 triumph.
Wells intercepted a cross-court pass -- one of three steals -- from Los Angeles' Kobe Bryant with 37 seconds left. After being fouled, he hit a free throw to put Portland ahead by seven and on its way to its seventh victory in its last eight home games.
"It was a great team effort," Wells said. "We've got so many guys who can put it in the hole. Without their inside presence, they are more penetration suspect."
The Lakers had won their last two regular-season games against the Blazers, including an 11-point home victory in the season opener on October 30. Los Angeles also swept Portland in three games in the 2001 playoffs as the Lakers successfully defended their NBA title.
Bryant led the Lakers with 28 points, but Los Angeles fell to 2-3 in its last five games, which have been played without O'Neal. The 7-1, 350-pound center is on the injured list with an arthritic big toe.
"It's tough obviously playing without the big fella," Bryant said. "Hopefully we'll get him back on Tuesday and we'll be able to start playing like the Lakers should play."
The Lakers are 7-6 overall without O'Neal, who was the MVP of the NBA Finals in each of the last two seasons.
Ruben Patterson came off the bench to collect 22 points on 9-of-11 shooting in just 27 minutes for Portland. He also contributed at the defensive end by guarding Bryant.
"Ever since training camp and practice, he's been arrogant," Patterson said of Bryant. "I just try to play physical with him. I can tell he was (frustrated). You know Kobe, he talks a lot."
When Patterson was on the floor at the same time as Bryant, the Lakers' All-Star guard was held to just five points.
"If we bumped into each other in the gym, we're playing one-on-one and I will demolish him," Bryant said. "But playing 5-on-5, that's a different mind set. ... He likes getting up to play me."
Patterson scored on a tip-in with 7:19 left in the game to knot the contest, 87-87, and ignite the Trail Blazers' 15-4 run.
Rasheed Wallace converted a pair of free throws 25 seconds later to put the Trail Blazers in front by two. The two-time All-Star recovered from his shooting woes early in the game to contribute 25 points.
Robert Horry tied it once again for Los Angeles with a 16-foot jumper, but Wallace put home a layup and then hit a free throw on the following possession to restore Portland's three-point advantage, 92-89.
"They're a lot like Miami. They are one of the best teams, but their record doesn't reflect it," Horry said of the Blazers. "They've got a lot of talent. We're not scoring as many from the inside and we're settling for the outside 'J.'"
After Lakers guard Derek Fisher missed from 3-point range, Damon Stoudamire dished out one of his season-high 14 assists to Wells, who nailed a jumper and gave Portland a 94-89 cushion with 5:22 left.
"We won a game and now we've got to build on it," said Stoudamire, who is averaging 8.3 assists in his last six games. "I just tried to get everybody in there. With Shaq not in there, its obviously going to be easier to penetrate."
Out of a timeout, Bryant scored to slice Los Angeles' deficit to 94-91.
Shawn Kemp was the next player to step up for Portland. The reserve forward made a basket from three feet, increasing the Blazers' lead to five with 4:43 to go.
Once a member of five straight NBA All-Star teams from 1993-97, Kemp reached double figures for the third straight game and finished with 12 points in 18 minutes.
"This was a game of runs," Blazers coach Maurice Cheeks said. "The point of our focus going in was to put the ball in the post, put the ball to guys in the post that had favorable matchups."
Los Angeles forward Rick Fox contributed to his team's demise, committing two of his three turnovers during a 32-second span.
Off Fox's bad pass, Wells hit a shot to give Portland a 98-91 advantage.
The 11-year veteran then was caught in his own half trying to bring the ball up the floor and was whistled for a backcourt violation as he tried to call a timeout.
"I thought we had a good game going there, then all of a sudden it disappeared," Lakers coach Phil Jackson said. "We made a couple of mistakes and the context of the game changed entirely."
Stoudamire then found Kemp for an 18-footer from the right corner to cap the Blazers' run and open a 100-91 cushion with just over four minutes to play.
Center Dale Davis also reached double figures. He had 12 points and 10 rebounds to record his fifth double-double in the last six games.