Raul Ibanez and Russell Martin each added a two-run shot for the Yankees, who opened a three-game series with their American League East rivals with a resounding win.
Phil Hughes (10-8) yielded three runs on five hits in a seven-inning effort, breaking a personal three-start winless streak. The right-hander walked one and struck out five for the AL East leaders, who improved to 60-39.
Boston starter Aaron Cook (2-4) was tagged for six runs on seven hits, lasting just four innings.
Carl Crawford, Dustin Pedroia and Jarrod Saltalamacchia each launched a bases-empty homer to account for Boston's scoring.