Blake finished with 10 rebounds and 11 assists for the Clippers, who ended with a 29-53 record to miss the postseason for the 15th time in 17 years.
Lamar Odom scored 21 points, Pau Gasol had 18 points and 17 rebounds, and Shannon Brown added 18 starting in place of Kobe Bryant.
Bryant sat out for the fourth time in five games to rest several injuries, including a swollen right knee and a broken finger on his right shooting hand. Andrew Bynum missed his 13th straight game with a strained left Achilles'.
Sasha Vujacic didn't return after spraining his right ankle in the second quarter. A Lakers spokesman said it was a severe sprain, although X-rays were negative. He'll have an MRI on Thursday.
Baron Davis sat out for the Clippers with a sprained right wrist. He was joined by Eric Gordon (viral infection).
The defending champion Lakers have lost six of 10 heading into the playoffs. They will face No. 8 seed Oklahoma City beginning Sunday at Staples.
Travis Outlaw added 14 points and 10 rebounds for the Clippers, who had seven players in double figures. They opened the season against the Lakers, losing 99-92.
The Clippers dominated the fourth quarter, hitting four 3-pointers — three by Blake — to pull away in what was a tight game until early in the third.
The Lakers trailed by three to start the third quarter, but were outscored 15-5 as the Clippers built the first of two 13-point leads. From there, the teams each scored 11 points to close the period, with the Clippers ahead 78-65.
Neither team led by more than five points in the first half. The Clippers led by that much over the final minutes of the second quarter until Josh Powell's basket cut the Lakers' deficit to 52-49 at the break.
NOTES: Since 2003-04, the Lakers are 23-26 without Bryant in the lineup. ... Rasual Butler was the only Clipper to appear in all 82 games, making him the first to do so since 2003-04. ... Jordan Farmar hit that mark for the Lakers when he entered with 1 second to play in the first half. ... The announced crowd of 20,044 was the Clippers' fifth sellout.