Jose Hernandez hit two solo homers for the Indians, who lost their fourth in a row after a nine-game winning streak.
Ken Griffey Jr., also hit two homers for the Reds, who broke a 4-4 tie in the ninth on an RBI double by Felipe Lopez off Bobby Howry (4-2).
Not even a return to interleague play could help the Indians emerge from a week-long funk that saw them lose three games to Boston, including two by one run.
If this hot-and-cold streak seems familiar, it is starting to be reminiscent of last August, when the Indians won 10 of 11 games to pull within one game of first place in the AL Central -- then quickly lost nine in a row and were never heard from again.
Griffey's second homer of the game, 14th of the season, and 515th of his career came off left-hander Scott Sauerbeck and tied the score, 4-4, in the eighth.
It was his first hit in 13 career at-bats against the left-hander.
Victor Martinez had an RBI single and Ronnie Belliard an RBI double for Cleveland in the first inning.
Tribe third baseman Aaron Boone was back in the lineup after missing two games with strep throat. He lost about 10 pounds during the illness and said he didn't eat because it was too painful to swallow anything during the ordeal.
Before the game, lefty Jason Stanford threw 45 pitches -- his first baseball-related activity at Jacobs Field this season. Stanford, who had elbow surgery last July, is not nearly ready to be activated, however. He suffered a setback in his rehab process six weeks ago when he tore some scar tissue in the elbow.
The Indians signed right-hander Jensen Lewis, a third-round pick and the 102nd overall selection out of Vanderbilt University. The pick was a compensatory selection from the San Francisco Giants for the free agent signing of shortstop Omar Vizquel.
Lewis, 21, had an 8-3 record and 2.62 ERA in 15 games as a junior this spring. He had been drafted by the Indians in the 33rd round in 2002 out of Cincinnati Anderson High School.
"I almost fell out of my chair when they called my name," said Lewis, who is a life-long Indians fan. He and his family lived about 35 miles southwest until moving to Cincinnati in 1990.
A communications major at Vanderbilt, he said his life's dream was to be the Indians' radio announcer. He spent the fifth inning of Friday's game against Cincinnati, with Tom Hamilton and Matt Underwood in the radio booth. "We better head for the unemployment line," joked Underwood during Lewis' impressive stint on the air.
General manager Mark Shapiro smiled at the thought. "We want him -- for his pitching," he said.
CLASS AAA BUFFALO (47-28) sent 12 men to bat in a six-run first inning and battered visiting Durham, 12-5. Jeff Liefer (.324) went 3-for-5 with three RBI and two runs. Dusty Wathan (.287) went 3-for-3 with two RBI, including a solo homer, his ninth. Mike Kinkade (.278) hit a two-run shot, his 10th, while Brandon Phillips (.259), Jake Gautreau (.292) and Ernie Young (.307) all had two hits apiece. Brian Tallet (5-2, 3.57 ERA) allowed four runs on six hits over six innings, striking out seven without a walk. Steve Watkins (4.57 ERA) yielded one run over two innings and Fernando Cabrera (0.89 ERA) gave up two hits and a walk, but struck out two in a scoreless ninth. Former Indians first baseman Josh Phelps hit his first homer for Durham since being demoted by Tampa Bay. Darnell McDonald (.304), who started the season at Buffalo, but was released by the Indians a couple of weeks ago, went 3-for-5 for the Bulls.
CLASS AA AKRON (40-33) scored twice in the first inning, but lost at Harrisburg, 3-2. The Aeros remained tied for first place in the Southern Division of the Eastern League despite their seventh loss in a row. Dan Denham (5-5, 3.52 ERA) gave up three runs over seven innings and Chris Cooper (2.37 ERA) worked one scoreless. The Aeros got two of their six hits in the first inning, when their two-run rally was helped by an error and hit batsman.
CLASS A KINSTON (2-2) got only a sixth-inning single by Luis Cotto (.188) and lost to visiting Salem, 3-0. The K-Tribe did load the bases in the fifth when both Brian Barton and Nathan Panther were hit by pitches and Ryan Goleski drew a one-out walk. But Caleb Brock grounded into a double play to end the threat. Nick Pesco (6-7, 3.99 ERA) allowed two runs over six innings, Mariano Gomez (3.00 ERA) gave up one run over two and Todd Pennington pitched a scoreless ninth.
CLASS A LAKE COUNTY (2-2) lost in 12 innings to visiting Delmarva, 8-5. Mike Butia (.252) went 3-for-5 with two RBI and Marshall Szabo (.222) hit a two-run homer, his third, to lead the Captains. Normally reliable closer Kieran Mattison (0-1, 2.84 ERA) gave up three hits, including a three-run homer, in the 12th to lose it. Starter Aaron Laffey (2.77 ERA) walked five and gave up four runs over 5 2/3 innings. T.J. Burton (3.92 ERA) yielded one run over 2 1/3 innings and Kyle Collins (2.39 ERA) pitched three scoreless.
CLASS A MAHONING VALLEY (2-2) won at Auburn, 7-6, as fourth-round draft pick Jordan Brown hit his first pro homer and went 2-for-4. Chris Clem hit a two-run homer, his first, and Matt Fornasiere (.412) went 2-for-5 with two RBI for the Scrappers. Justin Pekarek (1-0, 3.00 ERA) gave up two runs (one earned) over three innings of relief for the win. Starter Jim Deters gave up two hits and one walk, striking out two, over three innings in his pro debut. Dustin Roddy got the final two outs for his first save.
ROOKIE LEAGUE BURLINGTON (1-3) lost at Elizabethon, 8-4. Alfred Ard had two of the Indians' five hits and drove in two runs. Adam Hanson gave up eight runs, six earned, and eight hits over five innings. Gerson Mercedes struck out three without a walk and yielded one hit over three scoreless innings.