Holliday appeared in his first game since missing nearly a month with a back injury. Sidelined since Aug. 4, Holliday did not play in Friday's loss after appearing in 10 minor league rehab games.
He popped out and flied out in his first two at-bats against left-hander Drew Pomeranz (14-5). After the Yankees opened the sixth with a walk by Didi Gregorius and a single by Chase Headley, Holliday delivered.
The designated hitter drove a first-pitch fastball from Pomeranz 443 feet into the left field seats, giving the Yankees a 4-1 lead. It was Holliday's 17th homer and first since his game-tying blast at Fenway Park off Red Sox closer Craig Kimbrel in the ninth inning of a 16-inning win July 15.
Holliday's homer helped Masahiro Tanaka (11-10) get a third straight win since returning from a shoulder injury. He allowed one run and five hits in seven-plus innings, getting a loud ovation from the sellout crowd as he exited following a leadoff single in the eighth.
Tanaka allowed his only run when Eduardo Nunez doubled and scored on a wild pitch in the sixth.
The right-hander also was aided by his defense after the wild pitch. Gregorius made a tumbling catch on a liner by Mitch Moreland with the infield in and center fielder Aaron Hicks made a running catch near the warning track on Hanley Ramirez.
The combination of Holliday's power and Tanaka's effectiveness helped the Yankees get back to 4 1/2 games behind the first-place Red Sox in the American League East. New York has never trailed by more than 5 1/2 games this season.
Before the Red Sox tied the game and Holliday homered, Headley homered with one out in the second.
Pomeranz allowed four runs and eight hits in 5 1/3 innings, ending his career-high eight-game winning streak. He lost for the first time since lasting 4 1/3 innings June 11 against the Detroit Tigers.
NOTES: Yankees manager Joe Girardi said he did not hear from the league office about the appeals by Cs Gary Sanchez (four games) and Austin Romine (two games) for their suspensions for the Aug. 24 brawl in Detroit. The appeals were heard on Friday but no decision has been made yet. ... The Red Sox activated OF Jackie Bradley Jr. off the disabled list and he was 1-for-3. ... Girardi said 2B Starlin Castro was not in the lineup because he was at the dentist Saturday morning after losing a front tooth. ... Boston LHP David Price (left elbow inflammation) is slated for another bullpen session before Monday's game at Fenway Park. ... Yankees OF Aaron Hicks was lifted after the sixth inning due to a strained left oblique.