Six straight Giants reached base -- a walk and five hits -- in the eighth inning. Christian Arroyo's single tied the game and Gary Brown's single to left gave the Giants the lead.
While the Giants youngsters rallied for the win, it was the Cubs yougsters stealing the show in the early innings.
The Cubs lineup featured several of the team's top prospects as Kris Bryant (No. 1), Addison Russell (No. 2), Jorge Soler (No. 4) and Kyle Schwarber (No. 6) all started the game.
Schwarber, the Cubs' first-round pick in the 2014 Draft, provided the bulk of the offense and showed everyone why he's a top prospect with a grand slam to right field in the second.
Schwarber celebrated his 22nd birthday Thursday and finished the game 1-for-3.
"Just a fastball up and I didn't get it where I wanted to," Giants starter Ryan Vogelsong said.
For the third straight day, the Giants pitching staff was roughed up as the team has surrendered 24 runs over the first three games.
Ryan Vogelsong retired the side in order in the first inning -- something Madison Bumgarner and Jake Peavy were unable to do -- but then gave up a grand slam in the second and the Giants found themselves in a 4-0 hole.
Billy McKinney, in his first at-bat with the Cubs, got in on the home run party with a solo shot to right in the eighth.
Vogelsong, who will likely start the season in the bullpen, finished the game after two innings. The right-hander surrendered four runs on three hits. He also walked one and struck out one.
Vogelsong admitted that he lost his focus a bit in the second inning, but otherwise he thought his spring debut went well.
"Physically, it was good," Vogelsong said. "Just got to work on the mental side a little bit."
Opposite Vogelsong was Cubs right-hander Jacob Turner.
Turner, one of several pitchers fighting for the fifth spot in the Cubs rotation, was sharp in his first appearance of the spring. The right-hander struck out one and allowed one hit in two scoreless innings.
Cubs up next: Jon Lester makes his Cubs debut Friday against the Reds at Sloan Park in Mesa. The left-hander, who signed a six-year, $155 million contract, will be matched up with catcher David Ross, who was with him in Boston. No surprise, but Lester will be the Cubs' Opening Night starter on April 5. First pitch is scheduled for 2:05 p.m. CT, and the game can be heard on Cubs.com.