The slugger had gone 43 at-bats without a homer before launching a towering shot to left-center in the top of the sixth that gave the Red Sox a 2-1 lead.
Though Napoli had one torrid stretch in late May, he is hitting .204 on the season.
"I've been feeling a little bit better timing wise and seeing the ball better," said Napoli. "I'm just trying to go up there and give a tough at-bat every time. I don't know. I still have work to do. I've just got to try and keep it going."
Napoli will get at least the first part of Thursday's game off, as David Ortiz is set to start at first base at Turner Field.
But perhaps Napoli's homer will carry over if the Red Sox need him as a pinch-hitter.
"He had a couple of really good swings yesterday, follows it up with a ball he squares up today for the solo home run," said manager John Farrell. "Again, we're going to need every guy to hopefully find some traction with their own at-bats, recognizing it's not going to be a full nine every night. But when you can get contributions from different guys, that's what makes a team roll."
The long ball was Napoli's 10th, giving him double-digit homers in all 10 of his big league seasons.