Ross (5-4) nearly matched Hughes, allowing one run on three hits over seven innings, walking three and striking out eight.
''I've been able to get ahead of the hitters,'' Ross said.
Now if he only had the tonic to fix the Padres' hitters. Instead San Diego was shut out for the eighth time, tops in the majors.
Yes, Hughes was fantastic. And yes, this was another version of Groundhog Day for the Padres as they continue to struggle at the plate.
''They're out there battling,'' Ross said of the Padres' hitters. ''Hughes had a good game and I'm sure we're going to get them next time.''
Chris Parmelee's sacrifice fly to left in the sixth scored Joe Mauer and Plouffe hit his third home run in the eighth.
Glen Perkins pitched a perfect ninth to collect his 14th save in 16 chances.
Hughes (5-1) came over from the Yankees in the offseason, signing a $24 million, three-year deal. He won his fifth straight decision and didn't walk a batter for the fifth consecutive start, while striking out seven.
The Padres have lost two straight, scoring three runs in the two-game series against the Twins.
''The game is dominated by pitching right now,'' said Chase Headley, who had two hits. ''Good pitching beats good hitting and when a guy goes out there and pitches the way some of these guys are capable of you're going to have these games.''
They just happen more often for the Padres, who are averaging just over three runs per game.
''Whenever you are going through a time like this it seems like the longest and the worst,'' Headley said. ''I've been through some offensive struggles, but this one seems as tough as I've experience.''
Ross struck out eight for the third consecutive start, which is one off his season-high.
Mauer walked with one out in the sixth and stole second off Rene Rivera, who threw out three runners attempting to steal in his last start Sunday in Denver. Plouffe then hit a slow chopper to third and beat Headley's throw, with Mauer moving to third.
Mauer scored on Parmelee's sacrifice and Plouffe advanced to third on a throwing error by Headley. Ross then walked Kurt Suzuki, but escaped further damage when Jason Kubel flied out.
Ross breezed through the first five innings, allowing two singles and a walk while striking out six.
''He was nasty,'' Twins manager Ron Gardenhire said. ''He has a great slider, as advertised, a good changeup and a fastball that jumps on you. You have to respect that fastball so much; he was pretty darn good.''
Early on, Kubel was the only Twin who got into scoring position, after walking and stealing second in the second inning. Kubel was stranded when Danny Santana struck out, his first of four times, and Aaron Hicks grounded out.
The Padres looked poised to tie the game in the sixth when Headley and Yonder Alonso singled with no outs. But Jedd Gyorko and Cameron Maybin grounded out and Will Venable struck out.
The Padres, who had hits in each of the first four innings, threatened in the third with two outs when Seth Smith and Headley had consecutive singles. But Alonso, who was elevated to fourth in the order, flied to center.
Another Padres baserunner reached with two outs when Maybin collected his second hit in the fourth, but Rivera struck out to end the inning.
Smith had three of the Padres' eight hits.
''We did a poor job of getting guys in scoring position,'' Maybin said. ''We are all getting tired of it. ... It's frustrating.''
NOTES: Padres manager Bud Black left immediately after Wednesday's game and will miss Thursday's against the Cubs to attend daughter Jessie's graduation from the University of Maryland. Black will return for Friday's game. . OF Carlos Quentin remains sidelined with a groin injury, but will likely avoid the DL. . With 18 doubles, Plouffe is four doubles shy of last year's career high. . Ex-Twins 3B Corey Koskie and area scout John Wilson will represent the team at the first-year player draft on June 5 . Twins RHP Kyle Gibson (4-3, 4.20) faces Giants RHP Tim Lincecum (3-3, 4.74) to open a three-game series on Friday. The Padres send LHP Eric Stults (2-4, 4.50) against Cubs RHP Jake Arrieta (0-0, 2.70) on Thursday.