Napoli, Ortiz, Pedroia back Lackey in first win of the season for Sox
Dustin Pedroia went 4-for-5 and scored twice to help make a winner of John Lackey (1-0), who yielded two runs and three hits in six innings in his first start since winning the clinching Game 6 of last year's World Series.
Lackey struck out six against only one walk before Boston's bullpen delivered three clean innings.
Ubaldo Jimenez (0-1), making his first start for Baltimore, gave up four runs and five hits in six innings.
Nelson Cruz smacked a two-run homer in the fourth for the Orioles, who won Monday's season opener 2-1 thanks to Cruz's go-ahead blast in the seventh. Boston jumped in front 2-0 in the third inning in this one as Pedroia singled with one out and Ortiz followed with his first homer of the season.
Cruz tied things up one frame later, but the Red Sox promptly responded as Napoli homered to center on an 0-2 pitch by Jimenez.
The defending champions pushed across two more runs in the seventh as Baltimore opted to intentionally walk Ortiz with runners on second and third and one out, only to watch Napoli follow with a two-run single.
Boston relievers Edward Mujica and Junichi Tazawa logged the seventh and eight innings, respectively, before closer Koji Uehara worked around an error by Napoli in the ninth.
GAME NOTEBOOK: Boston CF Grady Sizemore went 0-for-4 with a strikeout after going 2-for-4 with a home run in the season opener - his first major league action since Sept. 22, 2011. ... Jimenez struck out six batters but also walked three and hit a batter. ... Baltimore OF Adam Jones struck out three times as part of an 0-for-4 night.