Facing Braves reliever Cristhian Martinez with a 0-1 count, Frazier got a sinker away that drifted back over the plate and drove it for an opposite-field homer that barely cleared the right-field fence.
"I played here for three years and I know the consequences of hard-hit balls or balls just missed," said ex-Red and current Braves catcher David Ross.
Frazier raised his arm in jubilation once he saw the ball land in the first row of seats. It was the first walk-off homer of his career.
"When I was going to first, I knew I had a lot of it," Frazier said. "At the same time, you're hoping it's a lot more than that. I didn't think I had all of it. Watching it rounding first, it just got over. That's fine with me."
A home run has accounted for nine of the Reds' 10 runs scored while winning the first three games of the four-game series.
With a season-high five-game winning streak, the Reds are also a season-high five games over .500 at 24-19.
"Right now, things are rolling," Reds starting pitcher Bronson Arroyo said. "We're getting clutch hits when we need them. We're pitching good enough to keep the score pretty low when we're not hitting. Hopefully that continues. We know at some point it will turn and it's not real fun."
In a no-decision for his 300th career start in the Majors, Arroyo pitched 6 2/3 innings and gave up one run and four hits with two walks and seven strikeouts. It was the club's fifth straight quality start.
Since a quality start has a baseline requirement of at least six innings and three or fewer earned runs, the quality of the stat has plenty of detractors. But there's no mistaking its benefit to the Reds. During the winning streak, the rotation is 4-0 with a 2.31 ERA.
"That's what usually happens in a winning streak," Reds manager Dusty Baker said. "You're either banging the ball unbelievably or you're pitching. Most of the time, you're pitching. One time through the rotation, and hopefully we will be two times through the rotation now. You keep getting that good pitching and you've got action."
The game was scoreless until the top of the fourth, when Dan Uggla led off by hitting a 1-0 pitch into the left-field seats for a home run. Arroyo rebounded well and retired 10 of his next 11 batters.
Braves starter Tommy Hanson retired a stretch of 12 in a row at one point, until a two-out single by Ryan Hanigan in the fifth. Zack Cozart started the sixth with a lined single into left field and Chris Heisey followed with a roller into right field. There was one out when Brandon Phillips worked an 0-2 count into a walk that loaded the bases. Jay Bruce grounded to second base and beat out a double play, which allowed Cozart to score the tying run.
Cincinnati, which was 0-for-8 with runners in scoring position and stranded seven runners, missed a prime chance to take the lead in the eighth. With runners on the corners and one out against Eric O'Flaherty, Bruce broke his bat and bounced into an inning-ending double play.
The Reds' bullpen and defense kept the team afloat in the late innings. Jose Arredondo followed Arroyo and pitched 1 1/3 scoreless innings. There were runners on first and second with two outs in the seventh when Michael Bourn's hard grounder to second base was knocked down by Phillips and bobbled briefly. In a spectacular play, Phillips made a successful force-play flip to Cozart at second from his back.
"That could have been a game-saver, because then the bases [would have been] loaded," Baker said. "We're accustomed to seeing Brandon doing stuff like that."
Aroldis Chapman pitched a perfect top of the ninth inning for Cincinnati with two strikeouts to earn the victory and improve to 4-0 and 24 1/3 innings without an earned run allowed.
Frazier hit two homers in a game against the Mets last Wednesday, but didn't catch fire. He was given a day off on Tuesday when Baker started Miguel Cairo against Atlanta.
"Miggy needed to play and Frazier needed to clear his head," Baker said.
Not wasting the time off, Frazier went to work with hitting coach Brook Jacoby.
"We looked at a lot of video," Frazier said. "I worked on putting a lot more weight on my back side a little bit. You can't say that's the reason you do better, but at the same time, it's the little things like that he's been helping me with. He understands and he's been helping me a lot so praise to him."