The 20-year-old Acuna became the youngest player in the majors when he was called up from Triple-A before the game. He went 1 for 5 and played left field.
Ozzie Albies, the second-youngest player in the bigs at 21, homered for Atlanta. He was hit by a pitch to begin the ninth and later scored on the go-ahead run on Johan Camargo's second double of the game.
Camargo drove in two runs and Ender Inciarte had three hits for the Braves, who led 3-0 after four innings. Acuna scored on Kurt Suzuki's two-out single in the eighth to make it 4-all.
Dan Winkler (1-0) pitched a perfect eighth and A.J. Minter worked the ninth for his first career save.
Kevin Shackelford (0-1) took the loss in his first appearance of the season since coming off the disabled list. The Reds dropped to 5-19, matching the 1931 team for the worst 24-game start in club history.
Joey Votto's two-run drive, his second homer in two nights, got the Reds on the board in the fifth.
Reds starter Brandon Finnegan, who opened the season on the disabled list with a strained left biceps, allowed two earned in five innings.
Braves starter Matt Wisler was roughed up for nine hit and four runs in five innings.
TRAINER'S ROOM
Reds: 3B Eugenio Suarez is 1 for 5 with a double and two walks in the first two games of his rehab assignment with Triple-A Louisville. He went on the disabled list on April 9 with a fractured right thumb.
UP NEXT
Braves: LHP Sean Newcomb (1-1, 3.74) is Atlanta's scheduled starter in Thursday's finale of the four-game series.
Reds: Hard-luck RHP Homer Bailey (0-3, 3.68), whose ERA is the best of Cincinnati's starters, is due to start the final game of Cincinnati's brief four-game homestand.