Griffey hit a go-ahead home run to move into a tie for 16th place on the career list, and the Reds rallied after Sosa hit two earlier in the game to beat the Baltimore Orioles 10-6 Sunday.
Griffey finished a triple short of the cycle. Rich Aurilia homered and drove in a season-high four runs for the Reds, who had 16 hits and wrapped up a 5-1 homestand after a 1-5 road trip that included a three-game sweep in Colorado.
Cincinnati scored 10 or more runs in four of the last five games of the homestand after just missing with nine in the opener. The Reds open a three-game series in Boston on Monday.
"It's nice to see," manager Dave Miley said. "It's something we've talked about. I thought we started swinging the bats better in the last two games at Colorado, and this whole homestand, we did a real good job. We need to bottle up this homestand and take it on the road to Boston for three days."
Griffey is tied with Eddie Matthews and Ernie Banks with 512 career home runs.
"All I want to do is win," Griffey said. "Like in the first game (of the series), when I bunted. If we could have tied it up and won, I would've been more excited than if I hit a homer. If I hit a homer, fine, but other hits count, too."
The Orioles, who lead the AL East, lost their second consecutive road series after opening the season by winning or splitting their first eight. They finished their longest road trip of the season with a 6-7 record.
"We had a chance to win a couple more, but the past two games, we didn't play very well," Baltimore manager Lee Mazzilli said.
Sosa hit a two-run homer in the second and added a solo shot in the third for his 68th career multihomer game, tying Barry Bonds for second on the career list. Babe Ruth had 72.
Sosa has eight homers this season and 582 for his career, one short of tying Mark McGwire for sixth place.
Griffey's two-run shot in the fifth gave the Reds a 6-4 lead.
Different players with 500 home runs have homered in the same game only three other times: Banks and Willie Mays on June 17, 1970; Hank Aaron and Mays on May 8, 1971; and Barry Bonds and Rafael Palmeiro last June 12.
Ramon Ortiz (2-4) shook off a five-hit, three-run second inning to earn his first win in six starts since May 12. He had been 0-3 with a blown save and a no-decision since.
Ortiz allowed just one other hit -- Sosa's second homer -- after the second and retired 12 of the last 13 batters he faced before leaving after seven innings.
"He gave up four runs relatively early, but he kept pitching and putting up zeros and gave us a chance to score some runs," Miley said.
Sidney Ponson (6-4) gave up seven runs and a season-high 11 hits, losing for the third time in his last four decisions.
"I wasn't making quality pitches," Ponson said. "When I did, the ball found a hole. I had nothing. My fastball was flat, and I didn't have my curveball."
Sosa followed Miguel Tejada's leadoff double with a 412-foot homer to help Baltimore take a 3-0 second-inning lead.
Aurilia tied the game with a three-run shot in the bottom of the inning.
"The pitch was down the middle to Rich, and he hit it like he's paid to do," Ponson said.
Sosa restored a one-run lead with a two-out homer to left in the third, but Sean Casey tied the game again with a one-out RBI single to right.
The Reds broke open the game with a three-run seventh, capped by a two-run single by Kenny Kelly, who was just called up from Triple-A Louisville on Sunday morning. The hit and RBIs were the first of his career.
- Sosa also has nine homers at Great American Ball Park, tying Houston's Lance Berkman and Milwaukee's Geoff Jenkins for the most by opposing players at the 3-year-old facility.
- Ponson's second-inning double was his first hit since he doubled at Arizona for San Francisco on Sept. 1, 2003.
- Ortiz recorded his first career hit in his 37th at-bat with a fourth-inning dribbler that third baseman Melvin Mora watched hug the third base line before hitting the bag.