The right-hander has failed to last past the fifth inning in three 2014 outings, but the Reds have won nine straight when he starts versus the Cubs.
Bailey (0-1, 8.16 ERA) turned in a second straight five-inning stint Monday, allowing five runs as he did not get a decision in an 8-7 loss to Pittsburgh. He struck out a season-high nine but surrendered a career-worst four homers.
The Reds (7-10) are 0-3 this year when Bailey starts, but he is 6-0 with a 3.39 ERA in his last nine outings against Chicago and 4-0 with a 2.62 ERA in his past five at Wrigley Field.
The Cubs (5-11) may want to load their lineup with left-handed hitters, who are batting .538 off Bailey. Chicago may also want to swing early, since hitters are 4 for 8 when putting Bailey's first pitch in play and 3 for 5 with two homers on 0-1 counts.
Nate Schierholtz figures to return to Chicago's lineup after sitting out Saturday's 8-4 win. The lefty-swinging outfielder is 7 for 15 off Bailey.
It's been a different story for Starlin Castro, a career .185 hitter against Bailey.
Chicago homered a season-best three times Saturday to end a season-high five-game slide after going three straight games without going deep. Welington Castillo, Mike Olt and Darwin Barney hit homers for the Cubs, who are now trying to win a series for the first time.
''I think the intensity was better,'' manager Rick Renteria said. ''Obviously, the results were better. But had the results not been there, I think the way they went about it was significantly better than yesterday.''
Cubs slugger Anthony Rizzo left in the eighth inning with back spasms. He said he tweaked it stretching for a pickoff throw and has had similar issues in the past.
Cincinnati fell for the second time in its last 18 games at Wrigley Field.
Chicago's Carlos Villanueva (1-3, 11.57) will try to bounce back from a disastrous outing last Saturday in St. Louis. He gave up a career-high nine runs over three-plus innings in a 10-4 loss, and didn't have any answers afterward.
"I didn't feel bad," Villanueva said. "I felt like I had good stuff. But they're a good team and they got me out of there quickly."
The right-hander has a career 4.12 ERA against the Reds, and he's 1-3 with a 2.98 ERA in seven starts. Joey Votto has given him the most trouble, going 7 for 18.
Brandon Phillips is 3 for 24 off Villanueva. He went 0 for 5 on Saturday after leaving Friday's 4-1 victory in the third inning due to back spasms.
Catcher Devin Mesoraco doubled twice Saturday and is 14 for 29 while hitting safely in all eight of his games.
Billy Hamilton is 4 for 9 in this series and has four stolen bases in his last three games.
Fellow outfielder Ryan Ludwick will likely miss a second straight game with a bruised toe.