Arenado sent the Coors Field crowd into bedlam with his single into center field to drive in Josh Rutledge from second and give the Rockies a 2-1 victory over the Giants.
The single off Jeremy Affeldt (1-4) was the second career game-ending RBI hit for Arenado, who won a game over the Padres on June 7 with a home run.
The Rockies (41-41) have started a stretch of 16 games against the National League West with two victories over the Giants. Saturday's victory pulled them to two games behind the West-leading D-backs.
"Through the long season like it is, teams go up and down and when they go up, they win nine, 10 in a row -- and we haven't had that streak yet," Rockies catcher Yorvit Torrealba said. "We're just waiting to get hot."
Meanwhile, the defending World Series champion Giants (38-42) have lost a season-high six straight.
"It's not a good streak, and I'll leave it at that," Giants manager Bruce Bochy said.
Also, Michael Cuddyer's RBI single in the first inning extended his hit streak to 26 games, longest in the Majors this season and longest since Jose Reyes, then with the Marlins, went 26 straight July 13 to Aug. 8 of last season. Cuddyer has reached in 45 straight games, which is the longest such run since Kevin Millar reached in 52 straight for the Orioles from June 20 to Aug. 25, 2011.
After Jhoulys Chacin threw eight scoreless innings in a 4-1 victory over the Giants on Friday night, the Rockies needed to work even harder to win Saturday's pitcher-dominated contest.
The Rockies scored off Giants starter Matt Cain in the first inning, placed two on base but didn't score in the second, then watched Cain retire 20 straight before leaving after the eighth.
"I started making good pitches and started trying to get ahead of guys," said Cain, who held the Rockies to three hits and struck out five.
Rockies starter Jorge De La Rosa held the Giants to one run and six hits in six innings before leaving with a bruised left thumb -- an issue that has bothered him for three starts now, although he has pitched well in each. The Rockies have won two of the games, and in the other De La Rosa gave up one hit in seven scoreless innings but the Rockies lost.
"I know what kind of pitcher Cain is, and I just tried to keep the game close the whole time," De La Rosa said.
A bullpen relay team of Wilton Lopez, Josh Outman, Matt Belisle and Rafael Betancourt (2-3) pitched the Rockies to the end without any additional runs.
The finish was especially hopeful for Belisle, who threw 1 1/3 clean innings, and Betancourt, who struck out one in a 1-2-3 top of the ninth. Belisle was 0-3 with a 16.20 ERA in his previous seven games. Betancourt was making his first appearance since May 31, before he was placed on the 15-day disabled list with a right groin strain.
"We've said all year we're a very competitive bunch and we understand not to overemphasize series but we know this is a series and all the way to the break a stretch where we want to be in control," Belisle said.
With two down in the ninth, Affeldt walked Todd Helton. Rutledge ran for Helton and stole second to set up Arenado's game-winner.
"Nolan's one of those guys that likes to be in the box when the game's on the line," Rockies manager Walt Weiss said. "You don't see that with young players very often. He's got a lot of energy but in those situations he's able to slow the game down and be the guy."
Arenado said, "I try to enjoy those situations as much as I can. It's tough. It's funny. You play this game for a while and you're going to be in situations like this, and you're going to fail most of the time. But you go through it. Today was a good day."