Before back-to-back losses to end the series, the Padres had won nine in a row against the Marlins in Miami.
The walk-off marked the ninth time the Padres have lost a game in the last at-bat, and the second time they have been the victim of a walk-off hit during their current road trip. San Diego is 2-5 in extra-inning games this year.
Jose Reyes led off the 10th inning with a bloop double off Brach. After the reliever intentionally walked Carlos Lee, Ruggiano lined a single through the left side to score Reyes. Ruggiano's game-winning hit helped break a 4-4 tie and put to waste a late-inning rally by the Padres.
"I knew who was on second," Ruggiano said. "I might have been swinging too hard the first couple of swings, but I knew once it was through that [Reyes] was scoring."
Yonder Alonso hit a game-tying, two-run homer to right field off former Padres reliever Edward Mujica in the eighth. In his last 23 games, Alonso has driven in 18 runs.
"Very seldom do rookies come in and make bold statements," Black said. "It happens, but the majority of the time it takes some time for them to settle into the game. He's had some nice stretches. This was a good series for him, so let's hope he continues that into Cincinnati."
Alonso finished the series back in Miami, where he grew up and attended the University of Miami, with five RBIs after breaking a 0-for-21 slump Friday.
"Obviously wish we had more wins, but personally ... it was pretty good," Alonso said. "It was fun, I enjoyed it a lot. It was everything I was hoping for."
His homer Sunday came shortly after the Padres blew a two-run lead of their own.
The Padres were up heading into the sixth, but Clayton Richard gave up a pair of singles to Emilio Bonifacio and Reyes to put runners on the corners and end his night. Dale Thayer relieved Richard and allowed the inherited runners to score on a Lee sacrifice fly and a Ruggiano single.
Thayer then snapped a seven-inning scoreless streak when he surrendered a two-run triple to Donnie Murphy that gave Miami a two-run advantage.
Early on, the Padres took advantage of an uncharacteristically wild Josh Johnson, who tied a career high with six walks over five innings in what could be his last start for the Marlins, with Tuesday's non-waiver Trade Deadline looming.
Johnson issued a two-out walk to Alexi Amarista in the third, and Mark Kotsay followed with an RBI double to give the Padres an early lead.
San Diego again made Johnson pay for a pair of free passes in the fourth. Will Venable walked to lead off the inning, and John Baker reached on a Reyes error that should have been a routine double play. After Johnson walked Logan Forsythe to load the bases with no outs, Richard delivered a sacrifice fly to center field to make it a two-run game.
It was Richard's career-high sixth RBI of the year, and it was the 16th run driven in by the Padres' pitching staff this season. Richard didn't factor into the decision after pitching 5 1/3 innings and giving up two runs. The lefty snapped a streak of seven straight starts in which he allowed a home run.
"I thought his stuff was fine, but in general, his misses were over the heart of the plate," Black said. "He wasn't as pinpoint as we've seen him over the last handful of starts."
The Padres had ample opportunities to clinch the series and continue their post-All-Star break hot streak, but they stranded 14 men on base and went 2-for-11 with runners in scoring position Sunday as they dropped the first two series of their three-city road trip.
"We couldn't get guys in," Alonso said. "It goes like that sometimes. I think we pitched pretty good. Like I said, we just didn't get guys in."