BALTIMORE (AP) — Mike Napoli homered and drove in four runs, John Lackey allowed three hits in six innings and the Boston Red Sox spoiled the Baltimore debut of Ubaldo Jimenez by beating the Orioles 6-2 Wednesday night.

David Ortiz hit a two-run homer and Dustin Pedroia had four hits for the defending World Series champion Red Sox, now 1-1 after losing to Baltimore on opening day.

Nelson Cruz homered for the second time in two games for the Orioles, who mustered only six hits off Lackey and three relievers.

Ortiz connected in the third inning and Napoli made it 4-2 with a two-run shot in the fifth. Both homers came off Jimenez (0-1), who signed a four-year contract with the Orioles in February after winning 13 games with Cleveland last year.

Jimenez allowed four runs, five hits and three walks in six innings. He struck out six.

Lackey (1-0) gave up two runs, walked one and struck out six. The right-hander is 14-5 with a 3.34 ERA in 24 career starts against Baltimore.

Ortiz put the Red Sox up 2-0 in the third inning with a drive to right following a single by Pedroia. Ortiz was 0 for 7 lifetime against Jimenez before connecting.

Lackey gave up a leadoff single to Nick Markakis, then retired 11 straight before Chris Davis walked with two outs in the fourth. Cruz followed with an opposite-field drive to right on an 0-2 pitch.

Signed as a free agent in February, Cruz has accounted for all of Baltimore’s four runs this season — three RBIs and a run scored.

In the fifth, Jimenez hit Daniel Nava with a pitch and Napoli homered on an 0-2 count.

Boston pulled away in the seventh against Ryan Webb. After two singles and an intentional walk to Ortiz loaded the bases, Napoli lined a two-run single to left. Napoli had a major league-leading 31 RBIs last year with the bases loaded.

NOTES: Thursday night’s series finale features a duel of left-handers: Boston’s Felix Doubront against Wei-Yin Chen. … Baltimore LHP Johan Santana, seeking to rebound from shoulder surgery, threw 30 pitches off a full mound Wednesday in Florida. “It’s encouraging to see that Johan’s throwing all his pitches,” manager Buck Showalter said. … David Lough went 0 for 4 and Steve Lombardozzi went 1 for 3 in their Orioles debut. … Lackey has gone at least five innings in 23 of 24 starts against Baltimore.