Swisher's 26th home run of the year came off Orioles right-hander Koji Uehara with one out, as pinch-runner Eduardo Nunez danced off first base, having replaced Alex Rodriguez as the tying run.
Rodriguez lined a fastball into left field to begin the inning, and Swisher took note. His turn came an out later, and after watching two fastballs sail out of the strike zone, Swisher sat on a 2-0 heater and cranked it into the visitors' bullpen in left-center field.
"All you're really trying to do is drive something in the middle of the field," Swisher said. "I got a pitch up in the zone a little bit and was able to hit it out. ... I've never [homered] out over there. That's a first time for me, but the wind was blowing out that way."
The customary crush at home plate followed, with A.J. Burnett piling whipped cream heavily onto a towel to celebrate New York's fourth walk-off win of the year. Swisher also saved the Yankees from what would have been the Orioles' first three-game sweep in New York since 1986.
"If we lose today, then to me it's not a good homestand," said Yankees manager Joe Girardi. "Going 7-3 is a good homestand for us as we embark on a long road trip here. I thought it was a big swing."
"Swisher was looking heater, and he got it," Orioles catcher Matt Wieters said. "He was able to put a good swing on it. That's tough to do. Not too many guys square up Koji's heater that often."
Swisher's third career walk-off home run -- the last one came exactly one year ago, last Sept. 8 off the Rays' Dan Wheeler -- helped Ivan Nova avoid what could have been a tough-luck first Major League loss.
"That was the first time I saw a walk-off -- only on TV. I wished I could be out there watching," Nova said, grinning widely.
Offering little support for the 23-year-old Nova, New York was able to manage just one run in 6 1/3 innings against Baltimore's Brad Bergesen, who held the Yankees to four hits before departing.
"We needed a shot in the arm -- it seemed like we were sleepwalking there for a couple of nights," Rodriguez said.
Making his fourth Major League start, Nova was in command of the Orioles for a large part of the afternoon, retiring the first eight batters he faced and 12 of the first 14.
Baltimore got to Nova in the fifth inning, as Wieters -- given the green light on a 3-0 fastball -- went to the opposite field and slugged a two-run homer with Adam Jones aboard, depositing his 11th home run of the season into the left-field seating area.
"I was thinking of throwing a curveball, but I wasn't thinking he would swing," Nova said.
New York cracked through for a run in the third inning, when Curtis Granderson walked, stole second base and scored on Brett Gardner's double to the left-field wall. But that play also saw Gardner thrown out at third base trying to stretch the hit into a triple.
With support hard to come by against Bergesen, that blast was enough to sink Nova's chances of notching the victory. The right-hander hurled six innings of six-hit ball, walking two -- both intentionally -- and striking out six in an impressive performance Nova thought was his best so far.
"He's aggressive and always wants to follow you," catcher Francisco Cervelli said. "He's not afraid to throw in and throw every pitch. You put the sign [down] and he says, 'Yes. Let's go.' I think he's learning and has got more confidence. He's going to do well. He's going to have a long career in the big leagues."
New York's bullpen again turned in terrific work, with Dave Robertson, Boone Logan and winning pitcher Joba Chamberlain combining for three scoreless, hitless innings, striking out six.
There was a touch of intrigue, as a seventh-inning opportunity cried for Girardi to use Jorge Posada as a pinch-hitter while the Yankees threatened to at least take Nova off the hook.
After Marcus Thames notched a pinch-hit single off Jim Johnson, the light-hitting Cervelli grounded to third base on the first pitch he saw, ending the inning.
What was unsaid at the time was that Posada had already left the Stadium for a date with a neurologist at New York-Presbyterian Hospital, complaining of feeling "foggy" after taking a foul tip in Tuesday's game.
But the Yankees announced before sundown that examinations had cleared Posada to return to competitive play, more good news on an afternoon when Swisher had already provided a keynote moment to save the day.
"They came in and took the first two games in our home, and we didn't like that too much," Swisher said. "It took us a while to get it going, but it's just great to come out of this homestand with a big win."