The Braves won for the 75th time this season, most in the majors, and increased their lead in the National League East to a massive 15 1/2 games.
Upton's home run came off Ian Krol (1-1), who was tagged with the first loss of his major league career. Krol was making the 25th relief appearance of his rookie season.
Upton also drove in a run with a fielder's choice grounder in the third that put the Braves in front 2-0.
Scott Downs (4-3) was credited with the win after pitching the top of the 10th. He was the sixth Atlanta pitcher of the contest.