The rookie never made it out of the third inning, and after yielding eight runs in an 11-5 loss Saturday night, the only thing Matsuzaka delivered was an apology.
Rookie Scott Moore hit a grand slam to cap a seven-run third against Matsuzaka, and the Orioles ended a record 11-game home losing streak with a rare blowout.
Matsuzaka (14-12) gave up a career-high eight runs in his shortest outing in the big leagues. It was the shortest appearance by a Boston starter since Kyle Snyder pitched 2 1/3 innings against the Chicago White Sox on Sept. 6, 2006.
Matsuzaka has yielded at least five runs in three straight starts and in four of the last five.
"I'm the one guy dragging on this team a little bit," he said through an interpreter. "For that, I am very apologetic."
Tike Redman and Nick Markakis also homered for the Orioles, who won for only the third time in 18 games. The 11 consecutive home losses were the most for Baltimore since the franchise moved from St. Louis in 1954.
Baltimore had lost 26 of its last 34 games against Boston, including 15 of 19 at Camden Yards.
David Ortiz homered and hit two doubles for the Red Sox. The AL East-leaders led 4-1 before the Orioles rallied against Matsuzaka, making his 29th big league start.
"I think fatigue is really a factor for everybody," he said. "I can't really use fatigue as an excuse for myself."
Gustavo Molina led off the third inning with a single and took third on a double by Brian Roberts before a walk to Redman loaded the bases. Matsuzaka walked Markakis to force in a run, Miguel Tejada hit an RBI single and Kevin Millar walked to push across another run.
Matsuzaka then got two straight outs before Moore drove a 2-2 pitch into the center-field seats. Obtained in the Aug. 31 trade that sent Steve Trachsel to the Chicago Cubs, Moore was 0-for-13 this season -- including 0-for-8 with Baltimore -- before connecting.
"It took a lot just to try and relax and not be jumpy and make him come to me," Moore said. "He fell behind and I got a couple of pitches to hit. And I hit the fastball."
That concluded the Orioles' most productive inning of the season and ended the worst outing of Matsuzaka's major league career. The right-hander gave up six hits and three walks.
"The command of his fastball just kind of abandoned him," Boston manager Terry Francona said. "The velocity was not an issue."
Markakis added a two-run drive in a three-run fourth against Julian Tavarez. It was Markakis' 17th homer of the season, tying Tejada for the team lead.
Orioles starter Jon Leicester (1-1) allowed four runs and seven hits in five innings to earn his first big league win since Sept. 19, 2004, with the Cubs. It was his second career start; the last one came in 2005.
After allowing two runs in each of the first two innings, the right-hander settled down.
"Leicester putting up three zeroes in a row was probably a big difference in the game, along with the two-out grand slam," Orioles manager Dave Trembley said.
At the outset, it appeared that the Red Sox would be on the positive end of a rout. Boston started 6-for-12 with four doubles, a home run and a walk in taking a 4-1 lead.
Ortiz made it 2-0 in the first, hitting his 28th home run after a one-out single by Dustin Pedroia. Redman answered with a solo shot in the bottom half, his first home run since May 2005 with Pittsburgh.
The Red Sox added two more runs in the second. J.D. Drew hit a leadoff double and was at third with two outs before .237 hitter Julio Lugo and rookie Jacoby Ellsbury hit successive RBI doubles.
"I felt like I was throwing some good pitches that I could make a little better," Leicester said. "Things were happening quick and Dice-K just wasn't himself, or what we thought he was going to be, so I just had to keep the team around."