Matsuzaka, who helped the Boston Red Sox win the 2007 World Series, gave up five runs on six hits with one walk through five innings in his first start for the Mets, who signed him on Thursday to bolster an injury-depleted pitching rotation.
The 32-year-old right-hander had been released by the Cleveland Indians earlier in the week after spending all season with their top minor league team.
Austin Jackson, Torii Hunter and Miguel Cabrera each hit a home run as the Tigers beat the Mets 6-1.
The Tigers pounced on Matsuzaka early. He surrendered five runs in the first 1 2/3 innings, including a solo home run by Hunter in the first and Cabrera's homer in the second.
Cabrera and Hunter each had a pair of hits, with Cabrera driving in three runs for Detroit. Omar Infante also had two hits with a run scored.
The Mets were trailing 5-1 by the time Matsuzaka settled down and retired the last 10 batters he faced.
"I was a little bit more nervous than I expected to be," said Matsuzaka, who made 11 starts for the Red Sox last season after recovering from elbow surgery in 2011.
"Unfortunately, the first two innings decided the game, so it wasn't how I wanted it to go."