The Reds beat the Royals 5-1 in 10 innings Tuesday. The Royals have dropped eight of their past nine and are 22-45 overall. Only the Baltimore Orioles (19-47) have a worst record.
The Royals are 23 games below .500 for the first time since Sept. 13, 2011, when they were 63-86.
The Reds will go for a sweep of the two-game mini-series in Kansas City on Wednesday night. The Reds' victory Tuesday was their first over the Royals since June 12, 2010.
Mahle (4-6, 4.33 ERA) is 1-0 in two June starts, allowing 11 hits and two earned runs in 10 innings, while striking out 11 and walking four.
This will be Mahle's first time facing the Royals, but not his first time on the Kaufman Stadium mound. He threw a mound session before the 2013 draft when the Reds chose him in the seventh round.
"They had a high school workout," Mahle said. "Pitchers just threw a bullpen off the game mound; that was it. All the scouts were here."
He said never pitching against the Royals does not change his preparation.
"It's the same between every start," Mahle said. "I prepare to go out there and hit my spots and compete. It's a new team, and I've never seen them play before, so I'm going to do my homework and kind of make a game plan out of it."
He said he pitches not to the Royals' weaknesses, but his strengths.
"You always play to your own strength," he said. "We're going to find out what their weaknesses are and kind of find something there in the middle. I throw a lot of fastballs, but if there's a guy who likes a lot of fastballs, it kind of collides there.
"But, at the same time, if you hit spots, good things are going to happen. Obviously if you throw it down the middle, he's going to hit it, but if you hit a corner, or something like that, always if you make your pitch, good things are going to happen."
Good things happened to the Reds in the Tuesday victory. They trailed 1-0 entering the ninth, but Tucker Barnhart led off the inning with a blast off Kelvin Herrera that landed in the Royals' bullpen.
"That is against one of the best closers in the game, so that was huge," Reds manager Jim Riggleman said. "Both pitchers are pitching so good it's probably going to be a home-run type game. Nobody was putting a rally together. They got one and we got one, and our bullpen really did a great job."
Hammel (2-6, 5.12 ERA) is 2-1 with a 2.59 ERA in his last four starts after a 13-start winless streak in which he went 0-8 with a 7.28 ERA. He has issued two or fewer walks in 10 of his 13 starts this season.
Hammel is 0-3 with a 4.70 ERA in five home starts this year and is winless in his last seven Kauffman Stadium starts dating to Aug. 20.
He is 4-1 with a 3.42 ERA in 12 career outings (11 starts) against the Reds. He has won his last four starts against Cincinnati with a 0.75 ERA, but has not faced the Reds since 2016.