The 29-point difference tied the fifth-largest winning margin in Grizzlies' franchise history. Meanwhile, the Timberwolves were held to their lowest point total of the season and have lost eight of nine.
"It's one of those games you want to forget about. Not even talk about," said Minnesota forward Al Jefferson, who was held to a season-low nine points.
Memphis had six players in double figures to win for the third time in four games.
Stromile Swift added 16 points and 10 rebounds for Memphis, while Juan Carlos Navarro and Damon Stoudamire finished with 14 points apiece. Stoudamire hit all five of his shots from the field, including four outside the arc. Pau Gasol scored 13 points.
"I think we're taking small steps. That's all we can ask of ourselves," Swift said. "We're improving every day, every game. A lot of people may not be able to see it, but we can see it. So, we want to just continue to get better."
Rashad McCants led Minnesota with 18 points, while Sebastian Telfair scored 16. Antoine Walker added 13 points and nine rebounds, and Corey Brewer had 12 points for the Wolves, who shot 38 percent and had 18 turnovers.
Memphis had a season-high 12 blocks, including five by Darko Milicic and four by Swift.
"I thought we played the style of basketball we're capable of playing," Memphis coach Marc Iavaroni said. "We played with a lot of energy and a lot of intensity on defense."
The Grizzlies carried a 24-point lead into the fourth, and the lead grew to as many as 37.
Telfair and Walker combined to shoot 13-of-33 from the field, and Ryan Gomes missed six of his seven shots. Minnesota was short-handed at guard with injuries to Randy Foye and Marko Jaric, leaving Telfair to play a season-high 43 minutes.
Even Jefferson was not at full strength from a left knee injury he re-aggravated in Friday night's loss to San Antonio.
"This was our worst performance of the year," Minnesota coach Randy Wittman said, "either because we felt sorry for ourselves or because of where we are injury-wise. We didn't come out with any purpose or thought of winning that game."
Memphis shot 49 percent in the first half, including 7-of-14 from 3-point range, to carry a 49-40 lead into the dressing room. No players were in double figures for either team, but Miller did have nine points and 11 rebounds.
The Grizzlies, with the return of 7-foot center Milicic, had a height advantage over the depleted Timberwolves, whose tallest starter was 6-10 Jefferson.
Stoudamire gave Memphis an early spark, connecting on his first three shots from outside the arc. Memphis led by as many as 16 in the first half.
Walker had nine points off the bench in the first half for Minnesota.
Memphis continued to build the cushion in the third quarter, hitting 13 of 21 shots and extending the lead to as many as 26 before carrying a 79-55 lead into the fourth.
"We put our foot on them, and we didn't pick it up," Gay said. "The whole thing was just straight pressure."
For the Timberwolves, it was an example of how the team needs to regroup. Minnesota has won only two of its first 15 games, the worst record in the league.
"We know how much talent we have in this locker room, and how we compete and how we play in practice," Gomes said. "It's just not going the way we think it should be going."
- Rookie G Brewer made his second start.
- Milicic was back in the starting lineup after missing six games with a sprained left thumb.
- Walker drew a technical foul for arguing a no-call midway through the second quarter.
- Stoudamire lofted a shot from beyond midcourt well after the buzzer for halftime that made it through. Officials did review the play just to make sure before ruling it no good.
- The Timberwolves were without C Theo Ratliff (sore right ankle) and G Foye, who is recovering from a stress reaction to the left patella. Jaric did not travel with the team after spraining his right foot and ankle in Friday night's game against San Antonio.
- Miller reached his fourth double-double early in the second half.