Griffey's two-out, two-run, pinch-hit home run to right-center field in the eighth inning pulled the Mariners even with the visiting D-backs, and an ensuing single by Chris Woodward and triple by Rob Johnson catapulted Seattle to a stunning 4-3 Interleague victory before 27,319 at Safeco Field.
But there was bad news to go with the good.
Left fielder Endy Chavez injured his right knee in a collision with shortstop Yuniesky Betancourt in the fifth inning and had to be removed from the field on a motorized cart. He will have an MRI exam on the knee on Saturday.
Held to seven singles and no runs for seven innings by D-backs starter Jon Garland, the Mariners came to life in the eighth against the Arizona bullpen. Russell Branyan greeted left-handed reliever Scott Schoeneweis with a leadoff home run to right field -- his 16th of the season -- and Adrian Beltre followed with a single to left off right-hander Tony Pena.
Two outs later, Beltre was standing on third base when Griffey emerged from the first-base dugout. The crowd roared its approval, and Junior responded with a first-pitch drive that landed well into the right-center-field seats.
"That was unbelievable," Johnson said. "The fans were going crazy when Branyan hit the home run, but when Junior stepped into the box it was as loud as I have heard it here, and the place wasn't even packed. I can't think of a better situation for something like that to happen.
"There wouldn't be this stadium if not for him. The people in this city love him and the players on this team love him. For something like that to happen is special."
The decibel level inside the House Griffey Built skyrocketed when the ball he hit soared high and majestic, landing about five rows deep.
"I was just looking for a pitch I could hit," Griffey said of his 618th career home run and sixth in a pinch-hit role. "I was not trying to do too much, get a pitch I could hit and hopefully hit it. I wasn't trying to hit a home run."
Griffey dropped his bat, watched the flight of the ball, and went into his home run trot.
"The only thing I was thinking about [going around the bases] is don't fall and embarrass yourself," Griffey said.
He made it around the bases without incident, disappeared into a dugout full of elated teammates and took his first curtain call of the season.
With the crowd's eyes still on Junior, Woodward drilled a single to left field, his second hit of the game, stole second and scored on Johnson's triple into the left-field corner.
A one-run lead was enough for closer David Aardsma to get his 13th save in 14 save chances, stranding the potential tying run at second base.
It was the 18th come-from-behind win for Seattle (33-34) this season, and the Mariners have now won five games when trailing after seven innings.
This might have been the most out-of-the-blue win yet and the Griffey home run was the talk of the postgame celebration.
"He jumped on that ball and it looked like he was 18," manager Don Wakamatsu said. "It was beautiful."
It was the first pinch-hit home run in Griffey's Hall of Fame career since Sept. 25, 2006, off Cubs left-hander Scott Eyre. It also was the first extra-base hit for a Mariners pinch-hitter this season.
Woodward, subbing for Jose Lopez at second base, scored when Johnson ripped a ball past third base and into the left-field corner for a triple.
"I was pretty pumped when I went into third," said Johnson, playing his first game since leaving the team last week to attend the funeral of his mother-in-law, who was killed in an automobile accident near Houston. "When I got to second, I saw the ball bounce around the corner, so I said I'm going to third."
It was his second triple of the season.
The win went to reliever Miguel Batista, who pitched one inning.
Most of the pitching praise went to starter Jarrod Washburn, who went seven innings, allowed three hits and settled for a no-decision. He still has not won a game since April 21 -- 12 starts ago.
It doesn't bother him nearly as much when the team wins.
"We won the game and that's all that matters," Washburn said. "That's a great way to win, to come back and have a big rally with two outs, Junior stepping in there. That's storybook stuff. It's cool."