Arizona pitcher Randall Delgado allowed four runs on five hits with one walk and two strikeouts over 3 2/3 innings.
Delgado got the start Tuesday in place of scheduled starter, Bronson Arroyo. Arroyo has a stiff back and was scratched late Monday. Delgado had been scheduled to throw in a simulated game Tuesday.
Each one of these Cactus League appearances are important for Delgado, who is out of Minor League options and will likely open the season in the bullpen, especially if Archie Bradley wins the job as the team's fifth starter.
San Diego pitcher Eric Stults struggled for the second time this spring. He allowed three runs on three hits with two walks in the first inning and needed 43 pitches to get three outs.
Quentin's home run off Delgado came in his first at-bat of the spring and his first at-bat since July 30 of last season, which was right about when he was shut down for the season with a right knee injury that eventually led to surgery.
"It was a good swing on the 3-0 pitch, that's how you do it on 3-0," Padres manager Bud Black said of Quentin. "He was looking fastball and put a good swing on it. He's felt good all spring building up to this game. We're happy where he's at after his surgery this offseason. He'll continue to build his endurance and stamina."
Paul Goldschmidt had two hits and scored three runs for the D-backs.
Up next: Patrick Corbin, who will start Opening Day in Sydney, Australia, gets the starting nod Wednesday against the Royals at 1:10 p.m. MT at Salt River Fields. The game will be the second of seven D-backs games this spring that will utilize the new instant replay challenge system.
Corey Brock is a reporter for MLB.com. Keep track of @FollowThePadres on Twitter. This story was not subject to the approval of Major League Baseball or its clubs.