Martell Webster led the Blazers with 21 points and 13 rebounds in handing Minnesota its 12th consecutive defeat.
Al Jefferson led Minnesota with 20 points, but the Timberwolves shot an anemic 37.7 percent from the field compared with 50 percent for the Blazers.
"Tonight we were knocking down our shots," said Blazers coach Nate McMillan.
Portland jumped ahead 23-14 in the first 12 minutes and led 40-37 at halftime. The Trail Blazers began the fourth quarter with a 22-6 run that ended all hopes of a Minnesota comeback. Webster scored six points in the outburst and added two consecutive shots to put Portland up 102-73 with 2:14 to play.