Ludwick's 13th long ball of the season secured the series win against the Cardinals and gave the Reds their fifth consecutive win.
Ludwick fell behind, 0-2, to Cardinals reliever Victor Marte, who entered the game after Marc Rzepczynski struck out Jay Bruce to open the inning.
Ludwick battled back, fouling off three consecutive pitches and taking three straight balls to force a full count. He then hit the ninth pitch of the at-bat for the Reds' seventh walk-off win of the season.
"When you're 0-2, that's what the game is about," said Reds manager Dusty Baker. "You've got to fight and battle and battle and battle. Foul off a pitch and take a pitch, and hopefully you can get one you can drive like he did. That was huge."
It was the fifth walk-off homer of Ludwick's career, but the 10-year veteran said doing it against his old team made it a little more pleasing.
"I'd be lying if I said it wasn't," Ludwick said. "I have a tremendous amount of respect for those guys over there. I would never do anything to show them up, but it feels good to beat them. I think that's the fifth time I've done it, and every one gets sweeter."
The game-winning homer continued Ludwick's hot streak of late. In his last 19 games, the 34-year-old is batting .319 with 22 hits, five home runs and nine RBIs.
The Reds' bullpen may have been the happiest group of all to get out with the win.
The pitching staff faced numerous jams in the game, and six pitchers were used.
Each reliever seemed to come on to save the inning for the pitcher before him. Reds starter Mike Leake lasted six-plus innings before leaving a jam for Sean Marshall to get out of. Marshall survived relatively unscathed, but left a bind for Logan Ondrusek, who returned the favor to Bill Bray.
Aroldis Chapman and Sam LeCure then each pitched one scoreless inning, with LeCure securing his third win of the season.
"That was a big-time grind all the way through," said LeCure, who combined with Chapman for four strikeouts in the final two innings. "It was nice to get some of the arms out of the bullpen and come in there after a few days off."
While both clubs left 11 runners on base, the Cardinals' chances came in bunches they couldn't take full advantage of.
"We had the opportunities and had some guys who come through in those situations often," said Cardinals manager Mike Matheny. "We just couldn't get that big hit."
The big hit on Saturday fell to the side of Cincinnati. And it was barely big enough.
"Boy, I didn't think that ball was high enough to get out of here. That was on time," Baker said. "That was great for national TV, great for our fans, and the fact that we picked up another game on them, man, that was sweet to win."