Patrick Wisdom led off the 10th with a single, sending ghost runner Willson Contreras to third. Jayson Heyward then unloaded a three-run walk-off home run.
The bone-shattering loss enabled the Cubs to take the series two games to one, the fifth straight series the Reds have lost two games to one.
And the San Diego Padres beat the Los Angeles Angels to move back to a one game lead over the Reds for the second wild card spot in the National League.
After a day off, the Reds open a three-game series Friday night in St. Louis and the Cardinals are only 2 1/2 games behind the Reds.
After Wisdom singled in the 10th, he took second uncontested, leaving first base open for a possible intentional walk. That would fill the bases and set up a force play at home and at every base.
Manager David Bell decided to let Brach pitch to Heyward, Brach’s second appearance since coming off the disabled list.
And Heyward hit one that was headed for Lake Michigan before it crash landed.
“It’s always a thought,” Bell said about an intentional walk. “Every situation is different, every hitter, everything is different. The disadvantage of walking the bases loaded is that you put the pitcher in a situation where a walk ends the game.”
And Brach averages five walks per nine innings and was 2-and-0 when Wisdom singled.
“There was a certain amount of likelihood that that could happen (a bases loaded walk),” Bell added. “You still have three outs to get so you take that risk out of the equation.”
The defeat ruined a practically perfect performance by Reds starter Vladimir Gutierrez. After two bad starts in a row, Gutierrez was poised and polished Wednesday, giving up one run and two hits over five innings and 85 pitches.
Ian Happ, the Cincinnati Reds stalker, hit his third home run in the series, one in each game, to give the Cubs a 1-0 lead in the first inning.
And that was all they were going to get off Gutierrez. The Cubs got only one more hit, a bunt by Sergio Alcantara in the second.
His only misfire was Happ’s home run and it came on a bad decision.
“The catcher (Tucker Barnhart) asked for a change-up right there and I shook him off,” said Gutierrez. “I wanted a fastball and I guess the batter (Happ) was waiting for a fastball. If I had thrown a change-up it would have been different.”
Of the Reds’ plight, with time slipping away — 22 games remaining —Gutierrez and the rest of the Reds realize it is time to perform some upticks.
“These are games that hurt a little bit. Obviously, it is a little frustrating for us,” he said. “This team is strong right now. We’re gonna come back. We have to look toward St. Louis right now and try to get some more wins.
Cubs starter Alec Mills kept the Reds just as silent, shutting them down until the fourth inning.
Joey Votto tied it, 1-1, with a two-out home run, his first homer in 17 games and his team-leading 29th of the season.
Tony Santillan replaced Gutierrez in the sixth and pitched two scoreless innings.
The Reds threatened to break the tie in the eighth. Jonathan India whacked a two-out double halfway up the ivy-covered brick wall in right center. But Tyler Naquin grounded out to second, leaving it at 1-1.
Luis Cessa pitched a 1-2-3 eighth and Mychal Givens matched him with a 1-2-3 ninth, sending the game into extra innings.
Pinch-runner Delino DeShields was the Reds 10th-inning ghost runner and he never budged. Kyle Farmer popped out, Barnhart struck out and Max Schrock struck out.
Then the Cubs put an end to it all.
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