Ortiz's fourth multihomer game of the season helped Boston to its third straight win and eighth in nine games. The Red Sox improved to 40-30, a season-high 10 games over .500.
"Ortiz never stops -- home run after home run," Arroyo said. "All my wins come off Ortiz's offense."
Arroyo (6-3) won his second straight start, allowing one run. He was aggressive with his fastball and said he threw more changeups than he has all season. It was his first start against Cleveland.
"They're a similar lineup to Texas with a lot of young prospects," Arroyo said. "I'm just more comfortable pitching against a younger lineup than I am against some of the more veteran guys."
Manny Ramirez added a two-run homer in the ninth to make it 9-2. He has six RBI in two games against his former team.
"There are days when Manny and David really pack some punch," Red Sox manager Terry Francona said. "That's why they're there."
The Red Sox have scored at least six runs in 10 of their last 11 games.
The Indians have lost two straight after a nine-game winning streak and have allowed 19 runs in the losses. It was their worst margin of defeat since a 9-0 loss at Minnesota on May 5.
Cleveland couldn't put together a solid inning against Arroyo, who walked one and struck out four.
Ortiz put Boston up 2-0 with a 419-foot shot to center in the first. He drove in Johnny Damon with a sacrifice fly in the second, then hit his 18th homer in the fifth on the first pitch from Kevin Millwood (2-5).
Millwood went six innings, allowing six runs, five earned, and seven hits in his second start since coming off the disabled list. It was his worst outing since April 16, when he gave up six runs in a loss to Minnesota.
"They have a tough lineup and I wasn't locating very well tonight," Millwood said. "I made some mistakes early on and it cost us."
It was the second straight rough outing for a Cleveland starter. C.C. Sabathia allowed a career-high nine runs on Monday.
"We haven't lost any momentum," Cleveland's Casey Blake said. "That's a great offensive team and it's tough to keep them down. No one on this team has lost any confidence."
Mark Bellhorn added a sacrifice fly and Damon hit an RBI-double in the sixth to make it 6-0.
"That's probably the play of the game," Francona said. "If that ball doesn't get caught, three runs probably score in a time when they're trying to come back."
Victor Martinez doubled, advanced on a groundout and scored on a wild pitch in the seventh to get the Indians on the scoreboard.
- The Red Sox have played 70 games this season without going to extra innings, a major league record, according to the Elias Sports Bureau. The previous mark of 69 games to start a season was set by the 2002 Chicago White Sox.
- 3B Cleveland's Aaron Boone was a late scratch from the lineup with strep throat. Blake started his second game at third.
- Damon has a 10-game hitting streak.
- Ortiz has 15 career multihomer games.
- C Jason Varitek of the Red Sox got his 800th career hit.
- Cleveland's Grady Sizemore singled in the eighth to extend his hitting streak to 11 games.
- The Red Sox have the same record as they did after 70 games last season.
- Ramirez's homer ties him with Jackie Jensen for 10th on the Red Sox career list with 170.