Brent Barry added 13 points for the streaking Spurs, who received 74 points from their reserves en route to winning for the 25th time in 28 games.
San Antonio shot 51.3 percent from the field -- including 14-of-29 from 3-point range -- and scored 100 points for the eighth time in 11 games. Tim Duncan had 12 points and 10 rebounds.
The Spurs were in control and that allowed Duncan and Ginobili to play just 21 minutes each and Tony Parker sat the remainder of the game after picking up two fouls in the first 1:44.
"Tony took a break tonight," said Spurs coach Gregg Popovich, whose team began the night two games behind the Phoenix Suns in the race for the Western Conference's No. 2 seed in the playoffs. The Suns hosted the Los Angeles Lakers later Friday.
"We're getting ready for the playoffs, and we played pretty well," Popovich said.
Mike James scored 23 points and Randy Foye had 16 for the Timberwolves, who have lost four consecutive games and seven straight at Target Center -- the team's worst home stretch since dropping a franchise-worst 14 consecutive in 1994.
Minnesota fell to 7-20 since the All-Star break.
The Timberwolves played a second consecutive game without star forward Kevin Garnett, who is out indefinitely while he gets a second opinion on his injured right quadriceps.
"When you're missing someone of his caliber of play, of course it hurts you," James said.
Minnesota had been struggling even when Garnett was in the lineup. Without him, the Timberwolves stood little chance against a Spurs team still fighting for playoff position.
Minnesota coach Randy Wittman has been using rookies Foye and Craig Smith and second-year player Rashad McCants increasingly in recent games, and the seasoned Spurs took advantage against the Timberwolves' inexperienced players.
"They're good," Wittman said of the Spurs. "Staying together as a group, and their coach in the same system. Over half this roster has been together a long time. You just go out and move. You don't have to call anything."
The Timberwolves' recent poor play and their decision to keep Garnett out have prompted some to say that the team is hoping to lose and assure that it keeps this year's first-round pick.
Minnesota entered the night tied for the eighth-worst record in the NBA. If the Wolves don't have a pick in the top 10 of the draft, they have to give their selection to the Los Angeles Clippers as part of the Sam Cassell-Marko Jaric trade two years ago.
Timberwolves players deny that the team isn't trying its hardest to win.
"You don't think about nothing like that," James said. "Especially for a draft pick because they're still rookies, no matter how good they are as college players. They still have to prove themselves on the next level."
The Spurs already have proved themselves, winning three NBA championships since 1999. San Antonio is hoping to improve upon its finish last season, when it lost in the Western Conference semifinals to the Dallas Mavericks.
The Spurs will play the Mavericks on Sunday in Dallas. The Mavericks already have clinched home-court advantage throughout the playoffs.
"We can't really focus on them because the only way we'll see them is in the Western Conference finals, so we just have to focus on ourselves," said Horry, who scored 11 points and shot 3-of-5 on 3-point attempts.
The Spurs cruised from the start as Ginobili and Duncan each scored 12 points to help them take a 55-39 lead at halftime.
San Antonio started the third quarter on a 14-6 run, with Horry's 3-pointer putting the Spurs ahead 69-45. San Antonio's lead never got below 15 points the rest of the way.
"Minnesota is not a team that at this point of the season is doing very well, so it probably makes things a little easier," Ginobili said. "We played a good game. We moved the ball. We didn't relax for that fact, so we've got to be pretty satisfied with it."
Spurs C Francisco Elson missed the game because of a sore left wrist he injured in practice. Horry started in his place. The team said Elson's injury doesn't appear serious. ... Timberwolves G Jaric sat out with injuries to both hands and his right knee. ... Minnesota dropped to 5-17 in games without Garnett in its history.