Baltimore finished with 18 of the 33 hits, the majority of the runs and five of eight walks in a 12-8 victory Sunday.
"I don't think I've seen a scoreboard where everybody on both teams had a hit," Orioles manager Buck Showalter said. "Day like today, ball's carrying. It was a very offensive day. It's a hard day to pitch. We just had a few more points than they did."
J.J. Hardy contributed his fourth career grand slam to a seven-run sixth inning, Nelson Cruz hit his major league-leading 35th home run and Ryan Flaherty also connected for the Orioles, who extended their AL East lead over the second-place New York Yankees to nine games.
"Each time you win, you feel like you put yourself in a position each and every day to be closer to the goal," said Caleb Joseph, who had a career-high four hits. "The goal is to play in October. "
"We scored plenty of runs," Twins manager Ron Gardenhire noted. "Pitching-wise, we just didn't stop them."
Ricky Nolasco (5-10) gave up eight runs and 12 hits over five-plus innings. He has lost four straight and is winless on the road since May 30.
"I feel like I beat myself today. No knock on them; they crushed the ball," Nolasco said. "This team is very dangerous, especially in this ballpark, and they showed that today."
"I think we've been very selective," Showalter said. "We've strung together a lot of good at-bats. Today we needed all of them."
Baltimore will seek to complete its first four-game home sweep of the Twins on Monday. The Orioles did, however, take all five games of a home series with Minnesota in 1966.
Wei-Yin Chen (14-4) allowed four runs and eight hits in 6 2/3 innings. The left-hander is 7-1 in 10 starts since June 28.
Minnesota made it interesting by scoring three runs in the ninth before Zach Britton served up a double-play ball for his 31st save.
The Orioles left the bases loaded in the first inning and stranded runners on the corners in the second. In the third, however, Nolasco couldn't escape.
Cruz homered, Chris Davis doubled and Hardy walked before Flaherty sent a 1-0 pitch over the 25-foot scoreboard in right field.
Plouffe homered in the fourth, but the Orioles went up 11-2 with their most productive inning of the year.
After Adam Jones doubled in two runs to chase Nolasco, Anthony Swarzak intentionally walked Davis to load the bases. On a 2-0 count, Hardy hit a drive into the left-field seats for his first slam since May 15, 2011.
"It's fun when everybody's contributing and helping the team," Hardy said.
Hardy didn't hit his first home run until June 21 but now has nine after hitting five in August.
"I'm seeing the ball better, not missing pitches when I get them," he said.
It was the sixth grand slam of the season for Baltimore, the second in the series.
Twins: RHP Phil Hughes (14-9), the winningest pitcher on the staff, starts Monday. He's the last Twins pitcher to beat the Orioles -- on May 4.
Orioles: Rookie Kevin Gausman (7-6) makes his first career start against Minnesota.
Twins: Sitting in his office and holding Baltimore's lineup card, manager Ron Gardenhire joked about the Orioles: "This team is so confident, they're going with (Saturday starting pitcher Chris) Tillman again today."
Orioles: Alejandro De Aza, acquired in a Saturday night trade with the White Sox, did not arrive by game time. So Lough started in LF. De Aza and Chen were added to the roster Sunday; C Steve Clevenger and P T.J. McFarland were optioned to Class A Aberdeen.
Santana and Kennys Vargas combined for 79 hits in August, most by a pair of rookie teammates in one month since Fred Lynn and Jim Rice totaled 77 for Boston in 1975.