Napoli stung Tanaka by hitting a solo home run with two outs in the ninth inning, lifting Jon Lester and the Red Sox over the Yankees 2-1 Saturday night.
Napoli had struck out in his previous two at-bats and was down 1-2 in the count before lining an opposite-field drive into the first row of the seats in right.
"He had me where he wanted me," Napoli said. "I was just looking for something up in the zone."
Napoli, who also homered off Tanaka at Fenway Park in late April, raised his right arm as he rounded first base and headed toward a dugout celebration.
Tanaka, the top winner in the majors and the AL ERA leader, turned to watch the ball sail, twisting his body when it cleared the wall.
"It was the worst thing I could've possibly done," Tanaka said through a translator.
Tanaka wanted to take a different approach than catcher Brian McCann.
"He asked for a splitter and for a slider, and I shook off both of them," he said.
Tanaka said he intended to throw a fastball out of the strike zone to set up a breaking ball.
Instead, Napoli hit it out of the park. His third home run in five games, and 10th shot overall, flew far enough reach the short porch.
"Power hitters are going to have the ability to hit to all fields. We all know that right field here is not very forgiving," Red Sox manager John Farrell said. "Last night, they hit one in the first row. Tonight, we did."
The Red Sox won for just the third time in nine games. The victory made the defending World Series champions 37-44 at the midpoint of the season -- it's the first time since 1997 that Boston has been under .500 at the halfway mark.
Lester (9-7) held the Yankees hitless until the sixth. He gave up an unearned run and five hits in eight innings, striking out six and walking two.
Koji Uehara pitched a perfect ninth for his 17th save in 18 chances.
Tanaka (11-3) allowed seven hits in a complete game, striking out eight and walking one.
The Yankees lost for the fifth time in seven games. Tanaka dropped consecutive starts for the first time in the majors.
The matchup between Lester and Tanaka shaped up as a pitchers' duel, and it certainly was. Lester improved to 13-6 lifetime against the Yankees, including a loss to Tanaka in Boston on April.
Lester and Uehara came through for a Red Sox team that has scored three runs or fewer in 12 of its last 14 games.
Napoli did his part, too, tagging Tanaka.
"He pitched pretty well to Nap all night," Lester said. "I'm guessing Nap put a pretty good swing on that ball right there. Luckily, we're in Yankee Stadium and not anywhere else and that ball goes out."
An odd sequence ended the Yankees eighth. Jacoby Ellsbury tried to steal second with two outs and the fans cheered when catcher David Ross' throw skipped into center field. As Ellsbury headed toward third, however, the crowd began to realize strike three had already been called on Mark Teixeira.
Ross homered in his second straight game, launching a drive far over the left-field fence in the third. Tanaka muttered to himself as Ross rounded the bases.
Lester, who threw a no-hitter against Kansas City in 2008, held the Yankees hitless until Brett Gardner bounced a leadoff single up the middle in the sixth.
Lester's bid was extended with two outs in the fifth when Yangervis Solarte was called out on a video review, taking away an infield single.
Pedroia opened the next inning with a single, and tried to test the arm of Ellsbury, his former teammate. The Yankees center fielder made an accurate throw and Pedroia was called safe, but he was ruled out after New York challenged the umpire's decision.
The Yankees scored in the third when Brian Roberts reached on shortstop Stephen Drew's error, Solarte was hit by a pitch, Gardner sacrificed and Jeter had an RBI grounder.
Of Boston's last 14 games, 10 have been decided by one run. The Red Sox are 6-4 in those games. ... The Red Sox are 26-26 at the new Yankee Stadium. ... Boston OF-INF Mike Carp (right foot) has started his rehab assignment at Triple-A Pawtucket. ... Yankees LHP CC Sabathia (right knee) made his first rehab start, pitching 2 1-3 innings for Class A Tampa and giving up two runs on three hits and a walk vs. Dunedin.