Ty Lawson scored 21 points and 10 assists and Danilo Gallinari hit five of his 20 in the final seconds to kill the Lakers' rally and send them to a third successive defeat.
Bryant did his best to rescue Los Angeles again by scoring 18 of his 29 points in the final quarter but the Lakers fell just short in front of a frustrated home crowd.
Los Angeles trailed by 10 midway through the fourth, although they fought back as Bryant twice made three-pointers to pull them within three in the final minute.
Gallinari drained a three of his own to halt the comeback with 13 seconds remaining and Denver (20-16) made four straight free throws to ice the game for their third win in four.
The Lakers (15-18) have now lost four of five and are tumbling down the standings under their new coach Mike D'Antoni and a star-studded roster.