Bryant led the Lakers with 32 points, including his team's final nine points. His 3-pointer with 54 seconds left tied the game.
Pau Gasol added 22 points and 13 rebounds for the Lakers, who won for the seventh time in their last eight road games.
The Grizzlies, who lost their fifth straight home game, were led by O.J. Mayo's 25 points. Zach Randolph scored 20 and grabbed 14 rebounds, his seventh straight double-double.
Mayo's two missed free throws with 18.8 seconds allowed the Lakers an opportunity to complete a comeback from nine points down early in the fourth quarter. Had Mayo made his free throws, the Grizzlies would have led by four.
Absent from the Lakers lineup for his longest stretch in five years, Bryant scored nine points in the opening quarter, including a four-point play, and triggered a late first-quarter run with two breakaway dunks to increase the Lakers' lead to 11.
Bryant last played Feb. 5 and Los Angeles went 4-1 without him.
The Grizzlies took their first lead early in the third quarter on a 3-pointer by Mayo for a 59-56 advantage and didn't trail again until Bryant's game-winning shot.
Bryant, averaging 42.5 points against Memphis in two previous games this season, began his late nine-point run with a jumper from the left wing with 2:23 to go to trim the Memphis lead to 95-92.
With Bryant scoring 17 of his points in the first half, the Lakers built several 14-point leads before settling for a 53-48 halftime advantage.
Notes
Randolph broke Pau Gasol's single-season franchise record for offensive rebounds (238). Playing in his 56th game of the season, Randolph grabbed four offensive rebounds to increase his total to 242. Gasol played for Memphis from 2001 to 2008.