The first of the two game-changing plays came on the day's first at-bat. Leadoff hitter Michael Bourn laid down a bunt on the fourth pitch of the game against the lefty Perkins, and reached safely when nobody in the infield could cover first base in time.
With Justin Morneau given the day off due to general soreness, Michael Cuddyer filled in at first. Cuddyer fielded the bunt and looked to the bag to relay to second baseman Matt Tolbert, but Tolbert, shifted closer to second in anticipation of a ground ball, couldn't beat Bourn to the base.
"We designed it that way," manager Ron Gardenhire said. "We know the guy's going to bunt off lefties. He did, and we just didn't get there."
"He's a speed guy. He bunts," Perkins said. "We knew what he was going to try to do. Nothing I can do about that. It happens."
Bourn then stole second base with teammate Jeff Keppinger at the plate. Keppinger drove in Bourn with a single up the middle for the game's first run.
The second miscue came next. Miguel Tejada sent a deep fly ball to the right-field corner. Just when it appeared that right fielder Jason Kubel had a bead on it, the ball bounced fair and over the wall in foul territory, leaving runners at second and third.
Kubel would leave after the third inning due to illness.
Houston took advantage of yet another opportunity with men in scoring position, as Carlos Lee's ground ball to second was enough to drive in Keppinger. Just two batters later, a sharp double down the left-field line brought around Tejada, giving the Astros a 3-0 lead before starter Wandy Rodriguez threw his first pitch of the game.
"I think the first inning pretty much tells the story today," Gardenhire said.
The series loss to the Astros marks the first time the Twins lost an Interleague series since May 2008, when they lost two of three games to the Rockies. It also marked the first time they lost an Interleague series at home since June 2007, when the Brewers stole a set at the Metrodome.
After Perkins was roughed up in the first inning -- he threw 19 pitches while giving up three runs -- he calmed down. He faced the minimum number of batters in three of the next four innings, and he did not allow another run in that span.
"I told him I was proud of him for going out there and still competing. That's big for young pitchers," catcher Mike Redmond said. "It's not all going to be roses out there for guys. Sometimes they're going to have to endure, and he did that today."
Perkins relied heavily on his fastball, but at times he was able to mix in a handful of other pitches that seemed to work after the first inning.
"I threw a lot of fastballs. I think I threw six and six on sliders and changeups," Perkins said. "[I had a] good sinker today, both sides of the plate. It was working, so we stuck with that. They were swinging early, so I didn't get a whole lot of deep counts to throw other pitches."
Perkins picked up his first loss in Interleague Play, having gone 3-0 in his previous four starts against the National League.
Offense was tough to come by for the Twins on Sunday, as Rodriguez limited them to just one run on two hits -- with the two hits a season low for the club. The lone run of the day came off the bat of Cuddyer, who launched his 11th home run of the season into left field. The homer came on the first pitch -- a changeup from Rodriguez -- of the bottom of the second inning.
"I was able to get good wood on it, and then he shut me down the rest of the day," said Cuddyer, who later struck out twice.
A Brian Buscher single in the seventh would prove to be Minnesota's only other hit of the day, as Rodriguez (6-6) struck out eight in seven innings.
"Their pitcher was pretty good," Gardenhire said. "He shut us down totally. That's not going to win too many games."
Houston tacked on one more in the seventh off Perkins when Tejada hit a sacrifice fly to left fielder Delmon Young. Bourn scored from third, crossing the plate for his second run of the day and a 4-1 Houston lead.
Lee was robbed of what would have been a two-run homer in the seventh. With Keppinger on first, Lee sent a drive to deep center, but speedy center fielder Carlos Gomez tracked it down at the wall, jumping to take away the homer.
Houston's Jose Valverde pitched a 1-2-3 ninth inning to record his fifth save of the season.