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 Kevin Youkilis and David Ortiz also connected for Boston, which won its fourth straight game and sent the Tigers to their fourth consecutive defeat.
Matsuzaka (5-0) won despite walking a career-worst eight batters in five innings, which also tied the major league high for walks this season. But he didn't allow a hit until Curtis Granderson's two-out RBI single in the fourth.
Craig Hanson, just recalled from the minors, gave up two runs in 1 2-3 innings. Hideki Okajima worked 1 1-3 scoreless innings before Jonathan Papelbon pitched the ninth for his 10th save in 10 chances.
The Red Sox walked 10 batters. Matsuzaka gave up one run and two hits with one strikeout, throwing 109 pitches.
Tigers starter Jeremy Bonderman (2-3) allowed four runs and seven hits in six innings, walking two and striking out four.
Lowell's two-run homer gave Boston a 2-0 lead in the second. The shot down the left-field line followed Manny Ramirez's leadoff double.
It was Lowell's first homer and RBI since last Sept. 29. He finished with three hits.
Lowell was sidelined from April 10-28 with a sprained left thumb. He led the team with 120 RBIs last season and was the World Series MVP against Colorado.
Youkilis made it 4-0 with his two-run shot in the fourth after Lowell led off with a double. Youkilis hit a drive over the left-field fence for his fourth homer.
Ortiz made it 5-1 with a run-scoring single in the seventh and added his sixth homer in the ninth.
Pinch-hitter Marcus Thames had a two-run single with two outs in the seventh for Detroit.
[Associated Press]
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