Pinch-hitter Jason Jaramillo ripped a double to left with one out off Reds reliever Bill Bray (5-3) before Ludwick came through with the walkoff single to center against Nick Masset, allowing pinch-runner Chase d'Arnaud to easily score from second.
Joel Hanrahan (1-4) earned the win despite plunking Todd Frazier to force in the tying run in the top half of the frame.
Trailing 3-2, the Reds rallied to tie the game in the top of the ninth. They loaded the bases with two outs. Hanrahan then went to 3-2 on Frazier before hitting him in the hand.
"I didn't have all my good stuff, but I tried to find a way to make it work," Hanrahan said. "I think I hit my first guy of the year. This game's funny."
The Pirates opened the scoring in the second inning when Ryan Doumit beat out an infield single to begin the frame and Jones homered to dead center field.
McCutchen smoked a two-out double in the third and scored on a base hit to right by Doumit.
The Reds put runners on second and third with two outs in the fourth, but were unable to score, as Ramon Hernandez grounded out to shortstop to end the inning.
Reds starter Edinson Volquez drew a one-out walk and Brandon Phillips followed with a single to put two men on again in the fifth and this time, the Reds got on the board courtesy of a double down the left field line by Votto.
"We didn't execute the fundamental things," Phillips said.
Janish singled in Frazier in the sixth.
In 20 games during September, Doumit is hitting .410...Pirates second baseman Neil Walker is in the midst of a career-best 51-game errorless streak...Reds outfielder Jay Bruce, who went 0-for-4, is one home run shy of 100 for his career...Prior to Friday's game, Cincinnati signed general manager Walt Jocketty to a three-year contract extension...McCutchen's triple in the fifth inning was his fifth of the season...Volquez gave up three runs on six hits over five innings...Pirates starter Jeff Locke gave up one run on six hits in 4 2/3 innings.