Cincinnati's Homer Bailey disappointed in his first few starts after agreeing to a generous extension, but he showed signs of coming around last time out.
Santana takes the mound opposite Bailey as the Braves open a three-game set against the visiting Reds on Friday night.
After failing to land a multiyear contract, Santana (2-0, 0.86 ERA) settled for a one-year, $14.1 million deal with Atlanta on March 14. The right-hander has exceeded expectations over his first three starts, holding opponents to a .178 average while striking out 24 and walking four in 21 innings.
Santana, off to his best start since opening 6-0 for the Angels in 2008, beat the New York Mets on Saturday as he gave up one run over seven innings in a 7-5 victory.
"He's a professional who goes about his business," manager Fredi Gonzalez told MLB's official website. "He makes great pitches with his breaking pitches and secondary pitches. He commands those pitches, and he doesn't give in."
Bailey (1-1, 5.75) had gone winless while compiling an 8.16 ERA over his first three outings before beating the Chicago Cubs on Sunday. The right-hander struck out eight over six scoreless innings in the 8-2 win.
"He hasn't been his normal, dominant self but his slider has gotten a lot better," manager Bryan Price said of Bailey, who signed a six-year, $105 million extension in February. "It seems like that pitch has really turned the corner and got him some big outs. ... That was a great silver lining in what was a solid outing, but not his best."
Despite Sunday's performance, Bailey knows he still has work to do. He's issuing 3.54 walks per nine innings, well above his 2.28 mark from the previous three seasons, and opponents are batting .341 against him.
"It's just kind of the ups and downs and I'm still trying to catch that rhythm," he said.
Bailey went 2-0 with a 3.42 ERA in his first four starts against the Braves before losing the last one, yielding four runs and 10 hits over six innings in a 5-2 defeat at Atlanta on July 13. Dan Uggla and Freddie Freeman are a combined 5 for 29 against Bailey, and Chris Johnson is 1 for 12.
Santana, meanwhile, will get his first look at Cincinnati. He'll try to build on another terrific outing from former Reds pitcher Aaron Harang, who struck out 11 over six innings in Wednesday's 3-1 victory over Miami.
Atlanta (14-7) owns baseball's lowest ERA at 2.10, including a 1.50 mark from its starters. The Braves' rotation has surrendered two earned runs or fewer in all but one game.
"You kind of feed off other guys, and you kind of hope they're doing the same thing," Harang said. "We're having a lot of fun right now."
So is Cincinnati (11-11), on the verge of climbing over .500 for the first time. The Reds, winners in seven of nine, are coming off three straight victories over Pittsburgh as the staff allowed four runs.
"Three series wins in a row, back to .500," said Ryan Ludwick, who doubled in both runs in Thursday's 2-1 victory. "If we keep getting pitching like that, we'll be back in this thing in a hurry."
Outfielder Billy Hamilton could return to the lineup after coming on as a pinch runner Thursday. The speedy rookie is hitting .355 with seven stolen bases over the last nine games.
"It's silly. He's different. He's a game-changer," Braves catcher Evan Gattis said. "You've just got to try to keep him off base."
Jay Bruce is batting .423 with two homers during a seven-game hitting streak at Turner Field.
Cincinnati went 3-4 against the Braves last season, splitting four games in Atlanta.