Griffey launched his 530th career home run and Lopez also connected Thursday as the Reds avoided a sweep with a 4-2 win over the San Francisco Giants.
The Reds won despite being outhit 10-5.
"Good placement," Griffey said. "The key is we were able to get some guys on base and the guys coming up behind them hit home runs."
Ramon Ortiz pitched a season-high 7 2/3 innings in helping prevent the Giants' first four-game sweep in Cincinnati since May 1983.
"To get five hits and win the ballgame is kind of unusual for this lineup," interim manager Jerry Narron said. "Griff's Griff, and Felipe has been swinging the bat better the last couple of days."
Giants closer Armando Benitez made his first appearance since injuring his right hamstring on April 26. Benitez, who needed surgery to repair two torn tendons, got the final two outs of the eighth.
"I felt good," Benitez said. "I was really happy to be out there. I was a little bit nervous, but not too nervous. I didn't worry about velocity. I was concentrating on location."
Giants manager Felipe Alou liked what he saw.
"The biggest thing is Benitez pitching," he said. "He worked his butt off to come back. I have a lot of respect for that guy and how he worked after that injury."
Ortiz (8-8) tied Aaron Harang for the team lead in wins, giving up two runs and nine hits. He had gone seven innings six times this year.
"With this team, if you can stay in the game for six or seven innings, you should win a lot of games, because we score a lot of runs," Ortiz said.
David Weathers pitched the last 1 1/3 innings for his 10th save in 12 opportunities. He gave up a single and a walk to start the ninth before getting two strikeouts and a groundout to tie Danny Graves, who is now with the Mets, for the club lead in saves.
Brett Tomko (7-13), who broke into the majors with the Reds in 1997, has lost his last three starts to set a career high for defeats in a season. His previous high was 12 with Cincinnati in 1998.
Tomko gave up five hits and four walks in six innings.
Griffey followed Rich Aurilia's first-inning walk with his 29th homer of the season, a two-run shot to center field. He has four home runs during a five-game hitting streak.
"A guy hits a 3-2 change and takes it to dead center, you've got to tip your cap," Tomko said. "The mistake was the walk before it."
Lopez hit his first homer in 86 at-bats since July 22, a two-run drive that put the Reds ahead 4-1 in the fourth.
Lopez, the only Reds All-Star this year, is 7-for-12 in his last three games after a 2-for-38 slump.
"I just got off my timing," he said. "After going good for that long, you figure coming back from a slump is easy, but it's not. Once you get off your timing, you start doing things differently."
J.T. Snow hit a solo home run for the Giants in fourth. It was his third homer of the season and first in 155 at-bats since June 2.
Pinch-hitter Lance Niekro snapped an 0-for-13 slump with an RBI single with two outs in the seventh.
- Tomko became the 337th pitcher to give up at least one home run to Griffey.
- Griffey increased his career RBI total to 1,529, tying him with Hall of Famer Tris Speaker for 39th place on the all-time list.
- Reds 1B Sean Casey returned to the starting lineup after missing a start on Wednesday with a strained left shoulder.
- The Giants expect to activate OF Moises Alou from the 15-day disabled list on Friday. Alou has been sidelined since Aug. 3 with a strained right hamstring.