BALTIMORE -- The Cleveland Indians couldn't have scripted a better start to the second half of the season.
The victory moved the Indians into first place in the AL Central, percentage points ahead of idle Detroit. Cleveland lost three straight against Toronto before the All-Star break to fall out of first for the first time since June 28.
"For us it was important because we finished the first half with three bad games against the Blue Jays," manager Manny Acta said. "We needed to get out there and put those three games behind us. It is important -- especially in our situation."
Cabrera, the second batter in the order, homered off Jeremy Guthrie (3-13) for a 1-0 lead. Travis Hafner then drew a walk, Santana hit the next pitch into the seats in center, and the Indians were on their way.
That made it easy for Justin Masterson (8-6) to improve to 3-0 in his last three starts.
"It was great for us to come out kind of firing," Masterson said. "It gave not only myself but the rest of us a lot of confidence, the ability to go back out there and get back in the rhythm of things that we've missed out in the last three days. Just have some fun."
Masterson gave up four runs and eight hits in six innings, striking out eight.
"I worked out of a few jams here and there," he said. "I felt in control most of the time."
Cleveland is 4-0 against Baltimore this season, outscoring the Orioles 28-11.
Nick Markakis drove in two runs for the Orioles, whose eight-game losing streak matches a season high. Baltimore is 1-13 since June 26.
"It's tough to put your team in the hole like that," said Guthrie, who allowed six runs, five hits and four walks in five-plus innings. Three of his major league-leading 13 losses have come during Baltimore's eight-game skid, including two in the last two games.
The Orioles were without manager Buck Showalter, who served a one-game suspension as part of the punishment handed out Thursday by Major League Baseball following a July 8 bench-clearing brawl in Boston. Bench coach John Russell ran the team while Showalter watched from a private box.
"It was fun. Obviously, you don't like the outcome," Russell said.
Mike Gonzalez, who appealed a three-game suspension stemming from the heated four-game series against the Red Sox, pitched a scoreless inning of relief. So did Kevin Gregg, who appealed his four-game suspension.
After getting to Guthrie early, the Indians made it 4-0 in the third when Michael Brantley doubled and scored on Santana's double. Guthrie avoided further damage by getting Orlando Cabrera to bounce into a double play with the bases loaded.
Markakis delivered a two-out, two-run single in the bottom half. But the Orioles wasted a two-out double by Felix Pie in the fourth, and Masterson retired Markakis and Adam Jones with runners at second and third in the fifth.
"We were in position to bridge the gap but weren't able to do it," Jones said.
Cleveland pulled away with a four-run sixth. After Grady Sizemore drew a leadoff walk, Orlando Cabrera broke an 0-for-18 slide with a single that ended Guthrie's night. Travis Buck then hit a sacrifice fly off Mark Hendrickson and Brantley singled in a run before Asdrubal Cabrera and Hafner hit RBI singles off Jason Berken.
The Orioles struck out a season-high 13 times, including five straight to end the game. ... Cleveland RHP Fausto Carmona threw 50 pitches in a simulated game Thursday and is poised to start one game of Monday's doubleheader in Minnesota. Carmona has been on the 15-day DL since July 3 with a strained right quadriceps. ... Orioles DH Vladimir Guerrero still felt pain from being hit by a pitch on the hand Sunday in Boston and was unavailable. All-Star catcher Matt Wieters took his place. ... Indians 3B Lonnie Chisenhall returned to the lineup after missing three games with a broken nasal bone, the result of being hit by a pitch. ... Hafner reached in all five plate appearances. He singled twice, walked twice and was hit by a pitch.