De'Andre Jordan and Chris Paul had 21 points apiece for the Clippers, who led by 25 in the first half. Los Angeles improved to 4-2 in its first game away from Staples Center.
Nicolas Batum had 23 points and nine rebounds for the Blazers, who mounted a second-half challenge but ultimately couldn't catch up.
Rookie Damian Lillard's pull-up jumper and Batum's 3-pointer helped Portland trim Los Angeles' lead to 75-69 late in the third quarter. Batum's driving layup at the buzzer made it 77-71 heading to the final period.
Portland closed to 86-82 on Meyers Leonard's alley-oop dunk from Batum, but the rally fizzled and Paul sent fans streaming for the doors when his jumper with 2:51 left extended the lead to 98-85.
Clippers star Blake Griffin had 10 rebounds and seven points while playing with a sleeve covering his right arm for the third straight game because of fluid in his elbow.
The Clippers played their first game away from Los Angeles, but did have a road win over the rival Lakers last Friday.
The victory over Portland came on the second night of back-to-back games. The Clippers handed San Antonio its first loss with a 106-84 victory on Wednesday night.
The Blazers (2-3) were coming off a 1-2 road trip that concluded with a 114-91 loss at Dallas on Monday.
Willie Green hit a 3-pointer to give the Clippers a 24-16 lead in the first quarter, and it quickly got ugly.
The Clippers grabbed a 43-28 lead on Matt Barnes' fast-break basket. Portland struggled offensively and Los Angeles led 53-30 after a 22-2 run—much of it with Griffin taking a break on the bench.
Luke Babbitt hit a 3-pointer for the Blazers at the halftime buzzer, but it didn't make much of a difference and the Clippers led 60-39 at the break.
Portland's reserves, averaging an NBA-low 12.8 points per game, had just eight points in the first half. Their counterparts with the Clippers scored 25.
Blazers coach Terry Stotts said the game was an interesting matchup between perennial All-Star Paul and rookie Lillard, the "old guard and the new guard."
Lillard, quickly building a reputation for his poise in his first year, scored 16 points.
NOTES: The Trail Blazers collected donations for the Red Cross to aid victims of Hurricane Sandy. Fans donated over $10,500, while Wells Fargo and the Paul G. Allen foundation each pledged $10,000 for a total of $30,500. ... The Clippers have won seven of their 32 games in Portland.