Bryant now has 23,354 career points and moved past Robert Parrish for 18th all-time in NBA history.
Pau Gasol had 21 points and nine boards while Josh Powell added 14 points and six boards off the bench for the Lakers, who have won two straight and six straight at home.
The Lakers are the first time in the NBA to hit the 50-win mark this season.
Ryan Gomes had 20 points while Kevin Love added 18 points and 14 rebounds for the Timberwolves, who have lost their last eight games.
The game was tight through the first several minutes of the first quarter, but Gasol sparked a 14-4 run to close the quarter with a basket and a free throw and scored six points during the burst to give the Lakers a 22-17 lead after 12 minutes.
A 7-0 burst in the second quarter, capped on a Sasha Vujacic three-pointer, helped Los Angeles take a 47-36 lead into the break.
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Minnesota scored the first seven points of the third to cut the deficit to 47-43 after Love put in a layup and a free throw less than two minutes in.
Los Angeles, though, responded a bit later with 10 straight points and held a 59-45 advantage with 6:49 left in the third after a Luke Walton layup.
A pair of three-balls from Bryant followed by a Powell tip-in helped the Lakers eventually take a 77-59 lead into the fourth quarter.
Minnesota never got closer than 16 points in the fourth quarter as the Lakers cruised to the win.