DENVER -- The experience was new and wonderfully different for Cristhian Adames.

He never previously had a walk-off hit in the majors, never had been mobbed by his happy teammates and never had Gatorade poured on his head.

That giddy moment unfolded at second base Wednesday night after Adames drove a pinch-hit, two-run double off the right-field wall with one out in the ninth inning to give the Colorado Rockies a 6-5 win over the San Francisco Giants in the rubber game of a three-game series.

The switch-hitting Adames doubled off veteran Joe Nathan to cap a three-run uprising and give the Rockies their third walk-off win of the season.

Nolan Arenado made it a one-run game when he led off the ninth with his 37th home of the season, driving closer Santiago Casilla's 1-2 slider into the stands in left-center field. Arenado flied out Tuesday night against Casilla, leaving him 1-for-11 against the Giants' closer.

"I've never really had success against Casilla," Arenado said. "He's always been tough for me. I tried to get the ball over the plate, tried to see it up and hit hard. That's it. He's tough, he's not comfortable, and he made a mistake and the ball came back over the plate."

After David Dahl took a third strike, Tom Murphy singled. Those two rookies hit back-to-back homers in the fourth that cut the Giants' lead to 4-3. Pinch hitter Charlie Blackmon, who missed the past four games with back stiffness, followed Murphy, and Giants manager Bruce Bochy brought in left-hander Josh Osich (1-3), who hit Blackmon in the back with a pitch.

When right-handed-hitting Nick Hundley came up to pinch hit, Bochy brought in Nathan. Left fielder Angel Pagan made a long run and an unsuccessful diving attempt for Hundley's fly ball that just eluded Pagan and loaded the bases. That brought up Adames, who is 14-for-49 (.286) as a pinch hitter with five RBIs after he belting Nathan's second pitch and second two-seam fastball to give the Rockies their first pinch-hit walk-off RBI of the season.

"Getting Hundley was obviously a big out," said Nathan, 41, a 16-year major league veteran who made his fifth appearance with the Giants.

"Unfortunately, I wasn't able to get him. Then the situation becomes even tougher. I kind of pulled on a two-seamer just trying to get a ground ball, trying to do anything I can to keep the ball on the ground. I kind of pulled one and left it in a bad spot. He put a swing on it, and the rest is history."

The Giants used nine pitchers, six in the final two innings. After starter Albert Suarez gave up three runs in five innings, five relievers combined to work the next three innings and get the game to Casilla in the ninth.

"The 'pen did a great job in the sixth, seventh and eighth," Bochy said. "Just couldn't hold on. You got to win games you're supposed to win. That's two that has gotten away from us here."

The loss left the Giants 2-5 on their road trip that concludes this weekend with three games at Arizona. San Francisco, which is a major-league-worst 17-32 since the All-Star break, fell five games behind the Los Angeles Dodgers in the National League West. The Giants are a half-game ahead of the St. Louis Cardinals and the New York Mets for the first NL wild-card spot.

Jordan Lyles (4-1) worked the ninth for the Rockies, who got a combined three scoreless innings from three relievers after starter Jorge De La Rosa gave up five runs in six innings.

Given a chance to start a second straight game, San Francisco center fielder Gorkys Hernandez took full advantage of the opportunity on his 29th birthday. He doubled in the second and scored on Brandon Belt's two-run homer that gave the Giants a 3-1 lead.

Hernandez, whom the Giants brought up from Triple-A on Aug. 23, hit his first homer to open the fourth and give the Giants a 4-1 lead.

Buster Posey put the Giants ahead in the first with a sacrifice fly, but the Rockies quickly tied the game in their half of the inning on Dahl's two-out single.

Hunter Pence's double put the Giants ahead 5-3 in the fifth, at which point Bochy began shuttling relievers in and out of the game.

"Up until the ninth, a lot of good things happened," Bochy said. "It would've been nice to tack on."

NOTES: Rockies 1B Gerardo Parra did not take the field in the second because of a right hamstring strain that he said would sideline him two or three days. He was injured stretching as far as he could for a long throw from 3B Nolan Arenado. ... RHP Jason Motte (right rotator cuff strain), who last pitched for the Rockies on July 25, threw 25 pitches to hitters, felt fine and will do so again Saturday. ... Rockies 1B Mark Reynolds will rejoin the team in San Diego after being with his wife for the birth of a child. ... RHP Jake Peavy (low back strain) was reinstated, giving the Giants 34 players on their active roster, including 19 pitchers. ... Giants 2B Joe Panik and CF Denard Span were given a second consecutive day off because both have struggled and the Rockies started a left-hander. ... Rockies 2B DJ LeMahieu extended his career-high on-base streak to 24 games with a single in the eighth.