Handed a 3-3 game in the eighth, Simon gave up the second of Khris Davis' two-run home runs and a solo shot to Scooter Gennett.
"It was uncharacteristic of Simon," Reds manager Dusty Baker said. "It may be a sign of fatigue, and also it's a sign that the guy over there, Davis, can hit. He has some pop. He's one of the best young players I've seen come into the league this year. They don't miss Ryan Braun much. I don't know if he could have done as much damage that he did today."
Simon has a 3.24 ERA, but came in with a 1.59 ERA over his previous nine appearances, allowing two runs over his last 11 2/3 innings. He last worked 2 1/3 scoreless innings in relief on Tuesday when Tony Cingrani's start was cut short by a back injury after 3 2/3 frames.
Baker's bullpen has been trying to catch up on rest ever since, as the Reds are in the backend of a streak of 20 games over 20 days.
"My bullpen is over-pitched," Baker said. "Some of the guys had a day off yesterday, but before that, they went 2 1/3 innings and three days in a row, like [J.J.] Hoover. We won the battle, but we might have lost the war against Arizona. [The Brewers] were off yesterday, and we have five more days in a row to go in this 20-days-in-a-row streak. Guys are busting it."
Reds starter Homer Bailey started the top of the sixth with Aramis Ramirez hitting a double to right-center field. Two batters later, with one out, Davis pushed a fastball that didn't go inside enough over the right-center field fence for a two-run homer that put Milwaukee up by one run.
"One of the mistakes I made ended up costing me," Bailey said. "It kind of happens in baseball. I probably should have done a better job of mixing my pitches in that at-bat. I'll know better next time.
"I was trying to go in. We went out on the pitch before. Everything else, we had gotten him out a couple of times going in on him. We figured we'd stay with the plan. We walked him [in the fourth] on a checked swing that was a very, very questionable call, to say the least."
In a no-decision, Bailey finished with three earned runs and six hits over six innings with two walks and five strikeouts.
Milwaukee's lead was short lived, as Brandon Phillips led off the Reds' sixth by hitting a 2-1 Yovani Gallardo pitch just out of Carlos Gomez's reach over the center-field fence for his 16th homer and 95th RBI of the season.
Following reliever Logan Ondrusek's scoreless seventh inning, Simon was pummeled by Milwaukee in the eighth. Aramis Ramirez led off with a walk and a pinch-runner was moved to second base on a sacrifice bunt. On the first pitch, Davis hit his second homer over the fence in center field.
For Davis, filling in for the suspended Braun, it was the first multi-homer game of his brief career. It was the first time Simon allowed multiple homers in a game since Sept. 18, 2011, while pitching for the Orioles.
"I was going up to the plate, thinking I was going to get a strike and just be aggressive with that runner in scoring position," Davis said of his at-bat vs. Simon.
Two batters later, with two outs, Gennett pulled a 1-0 pitch into the first row of right-field seats. The play was reviewed by umpires for nearly three minutes, but the homer was upheld. Simon was lifted when the next batter, Yuniesky Betancourt, hit a double to the wall in right-center field.
Rookie Nick Christiani took over for Simon, and after walking his first batter, Norichika Aoki, on four pitches, he retired the final four in a row.
On paper, this is a game the Reds are supposed to win. Cincinnati is 73-56, 17 games over .500, and 40-22 at Great American Ball Park. The Reds came in 5-1 vs. the Brewers at home. Fourth-place Milwaukee is 56-72 during a down season and has one of the worst road records in the National League at 26-37.
Bailey dismissed the fatigue factor as a reason for the loss.
"That's what we do, man. It's part of the game," he said. "We're not going to use that as an excuse. We're doing the same thing everybody else is. They have to do it, too. So do we. We lost this game. We'll come back tomorrow. It's not the end of the world."