Vargas' game-winning homer came on a 1-1 curveball from reliever Carlos Villanueva and helped the Twins win their second straight over the Cardinals, after St. Louis won both games at Busch Stadium.
"I go out there and I throw the pitch I want in basically the location I want and I get beat -- there's not much I can do," Villanueva said.
The walk-off win was keyed by Joe Mauer connecting on a game-tying solo homer to left field with two outs in the eighth off lefty reliever Kevin Siegrist.
"It was a couple big moments for guys looking for something to hopefully get jump-started," Twins manager Paul Molitor said of Mauer and Vargas. "We've talked about Joe, and I don't see the same as the outside does, because I'm around him all the time. But it was a big hit for him to have in that situation. And for Kennys to win a game, the goat to a hero couldn't have been more appropriate in that scenario today."
Twins right-hander Mike Pelfrey kept his club in the game, as he gave up just one run on four hits over eight innings. Pelfrey's lone mistake was giving up a solo homer to Jason Heyward with two outs in the seventh.
Cardinals lefty Jaime Garcia tossed six-plus scoreless innings, scattering just four hits and two walks. He pitched his way out of a jam in the first and settled down from there. He left in the seventh after allowing the first two batters to reach, but Cardinals reliever Seth Maness got out of a bases-loaded jam by getting Vargas to ground into an inning-ending double play.
"If I were [Garcia], I'd be pretty confident right now," Cardinals manager Mike Matheny said. "Every time he's going out there, he's taking us deep into the game and not giving [up] many opportunities."
MOMENTS THAT MATTERED
Mauer's blast ties it in the 8th: Minnesota's offense was quiet all afternoon until Mauer connected on a game-tying solo blast to left field. It was just Mauer's third homer of the year, but came in a big spot.
"I try to make them count when I do hit them," Mauer said with a smile. "It was exciting. It was nice to come up with that in that time of the game to tie the game and give us a chance to win." More >
Heyward's solo shot breaks tie: Heyward broke the scoreless tie in the seventh inning with a home run on a 3-1 pitch to right-center. Statcast™ projected that the ball landed 410 feet away from home plate. Heyward drove in the Cardinals' lone run on Wednesday, too.
"[Pelfrey] didn't make too many mistakes," Heyward said. "I feel like in every count, he made good pitches. He stuck to his strength and [threw] the heavy ball. It was off the barrel just enough."
Twins can't cash in: The Twins had the bases loaded with one out in the seventh after the Cardinals intentionally walked Kurt Suzuki following a sacrifice bunt from Eduardo Nunez. Vargas came to the plate, but couldn't come through, as Maness induced an inning-ending double play.
Garcia delivers solid outing: Garcia pitched in just seven games last year before having season-ending surgery. But the southpaw, who started his sixth game this season on Thursday, is healthy and going strong. He took a no-decision despite holding the Twins scoreless for six-plus innings. More >
SOUND SMART WITH YOUR FRIENDS
The walk-off homer was the first one for Vargas in his career and the first for the Twins since Trevor Plouffe connected on a walk-off blast against the Indians on April 17. It was also just the second walk-off win of any kind for Minnesota this year.
"It's a really good experience for these guys to play a really fundamentally sound team that knows how to win and compete with them. I don't know how we'll respond after winning these two games, but I think that's really valuable experience we gained." -- Molitor on the Twins splitting the four-game home-and-home series with the Cardinals
With Hunter at first base after a drawing a leadoff walk in the seventh, Eddie Rosario hit a slow roller to first baseman Mark Reynolds, who dove to first base to try to tag the bag before Rosario got there. First-base umpire Ed Hickox ruled Rosario was out, but the Twins challenged the call and it was overturned, giving Minnesota two runners on with nobody out.
WHAT'S NEXT Cardinals: The Cardinals will continue on their eight-game road trip, heading to Philadelphia for the weekend. Tyler Lyons will get the ball Friday when the Cardinals take on the Phillies at 6:05 p.m. CT. Lyons, filling in for the injured Lance Lynn, is 1-0 with a 5.00 ERA in four starts this season.
Twins: The Twins start a three-game Interleague series with the Cubs that begins on Friday at 7:10 p.m. CT. Right-hander Phil Hughes will make the start in the series opener at Target Field. He's struggled to replicate his success from last year, as he's 4-6 with a 4.79 ERA.
Rhett Bollinger is a reporter for MLB.com. Read his blog, Bollinger Beat, follow him on Twitter @RhettBollinger and listen to his podcast. Betsy Helfand is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.