Upton's 25th homer off Manny Parra (0-1) gave Atlanta its seventh victory in eight games.
David Hale (4-4) pitched out of a two-on threat in the 11th. Craig Kimbrel got the last three outs for his 38th save in 42 chances.
The Reds managed only two hits — a pair of singles by Billy Hamilton — in their seventh consecutive loss.