The Red Sox recorded their fifth straight win over Tampa Bay since a loss on Opening Day. Boston scored the decisive run in its final at bat on three occasions, including Tuesday's 6-5 victory in the opener of this three-game series.
Defensive miscues contributed to Boston's four-run eighth and left Tampa Bay manager Lou Piniella in a rage.
Travis Harper walked Todd Walker to lead off the eighth before Lance Carter (3-1) relieved. One out later, Manny Ramirez singled to left field, where Carl Crawford mistakenly threw to third and allowed Ramirez to take the extra base.
Ortiz, who enjoyed his first three-hit game for the Red Sox, singled to center to bring home two runs and tie it at 4-4. Pinch-runner Damian Jackson stole second and Shea Hillenbrand walked before Jackson was thrown out trying to steal third.
Giambi doubled off the wall in center field and Hillenbrand was able to score easily when shortstop Rey Ordonez bobbled the relay. Trot Nixon capped the inning with a run-scoring single.
Chad Fox (1-2) pitched the eighth for the win and Brandon Lyon worked the ninth for his first major league save.
Ordonez hit a two-run homer for the Devil Rays while Ramirez and Nomar Garciaparra had solo shots for Boston.