Moss' power stroke helped Dan Straily (4-2) win his third consecutive decision.
Moss hit his 10th homer in the second inning and 11th with a solo drive in the eighth. He also connected twice April 29 against the Angels. Of his five hits over 40 at-bats in his last 19 games, all are home runs.
John Jaso added an RBI double and a run-scoring single in Oakland's 10th consecutive home victory. The A's (40-27) won for the 20th time in 25 games and are off to their best start since 1990.
Brett Gardner drew a one-out walk in the sixth to end a stretch of 11 straight Yankees retired by Straily. Robinson Cano singled and Mark Teixeira hit a sacrifice fly.
New York missed a scoring chance during an odd sequence in the seventh.
Jayson Nix hit a two-out RBI single and stole second. With Nix as the potential tying run, Lyle Overbay came out to pinch-hit with a 1-0 count already against Austin Romine. A's manager Bob Melvin then made his own switch, to reliever Sean Doolittle.
Chris Stewart came on to pinch-hit for Overbay, who never reached the batter's box but was credited for appearing in the game. Stewart struck out to end the inning.
Doolittle then pitched a perfect eighth before Grant Balfour finished for his 17th save of the season and 35th in a row dating to April 29, 2012. He retired Nix on a broken-bat comebacker to end it with runners on first and second.
Straily, coming off a pair of no-decisions, allowed two or fewer runs for the fourth time in five outings. He gave up two runs and three hits in 6 2-3 innings.
Oakland owns its longest unbeaten streak at home since another 10-game run from Aug.
Moss sent the first pitch he saw from Phil Hughes (3-5) over the right-field scoreboard in the second following Josh Reddick's leadoff single.
After a 1-2-3 fourth inning, Hughes issued a leadoff walk to Eric Sogard in the fifth. Jaso's double one out later and another walk to Seth Smith ended the right-hander's night.
Hughes walked a season-high five and lost for the third time in four decisions. He allowed three runs on four hits and struck out three in 4 1-3 innings. He hadn't walked more than two batters all season before this game.
The Yankees haven't hit a home run in a season-high five straight games—the club's longest drought since also going five games from May 17-21, 2006.
NOTES: Yankees RHP Michael Pineda, working his way back from shoulder surgery 14 months ago, threw a 75-pitch bullpen session. He had been set to pitch in a minor league game this weekend but instead will throw a simulated game Friday at the team's complex in Tampa, Fla. "This way we can control it," manager Joe Girardi said. "The other day he had one long inning. If Tampa would have been at home he would have pitched in that game." ... A's CF Coco Crisp is nursing a bruised heel—which happened sometime after his first-inning home run Tuesday before his next at-bat—and sat out after hitting home runs the previous two games. "He felt it when he got up this morning," Melvin said. "He felt better when he got to the park and got some treatment. We won't take any chances with him but if he comes in tomorrow and feels like he's close to 100 percent, there's the potential for him to play." ... A's LF Yoenis Cespedes also was sidelined because of tightness in his left hamstring that forced him to leave after the second inning Tuesday. ... RHP Jarrod Parker (5-6) pitches the series finale for the A's on Thursday afternoon opposite Hiroki Kuroda (6-5). ... Gardner failed to get a hit for just the third time in 19 games since May 24.