Griffey connected off Matt Capps (1-3), who started the ninth with a 3-2 lead but couldn't get an out. David Ross opened with a double, and Griffey - who got into the game as a defensive replacement in the ninth - hit the second pitch he saw into the seats in right-center.
Francisco Cordero (3-1) escaped a bases-loaded threat in the ninth, helping the Reds get the better of a matchup between the NL Central's bottom two teams.
When he saw he was out of the starting lineup, Griffey playfully asked Darren Baker - son of manager Dusty - why he was out of the lineup. The 9-year-old responded, "You can't hit lefties, and you're old!"
He showed he still has a little left in his 38-year-old body.