SAN FRANCISCO -- The Giants opened their biggest series of the season with their best player back in the fold, and it didn’t take long for him to make an impact.   

Mike Yastrzemski returned to the starting lineup for the first time since Sept. 17 and crushed a majestic, two-run home run into McCovey Cove to cap a four-run fourth inning that lifted the Giants to a 5-4 win in Game 1 of Friday’s doubleheader against the Padres at Oracle Park.

• Box score

Brandon Crawford and Wilmer Flores also homered for the Giants (29-28), who retained their hold on a National League Wild Card spot with three games left to play. Left-hander Tyler Anderson earned the win after holding the Padres to two runs on five hits over six-plus innings.

The Padres made it interesting by scoring three runs in the seventh to pull within one, but Tony Watson recovered and retired Eric Hosmer, Wil Myers and Austin Nola to end the game.

The Giants received an emotional boost before the game with the return of Yastrzemski, who missed six games with a mild calf strain. He made a pinch-hit appearance in the club’s 5-4 loss to the Rockies on Thursday, flying out to center field, and received medical clearance to play right field and bat leadoff against Padres right-hander Chris Paddack on Friday.

The Padres opened the scoring on Tommy Pham’s RBI double in the second inning, but the Giants tied the game, 1-1, with Crawford’s seventh home run of the year, a 419-foot shot to straightaway center field.

Flores sparked the Giants’ key four-run rally with a leadoff homer off Paddack in the fourth, driving a 3-2 fastball out to left-center field to put the Giants ahead, 2-1. It was his 10th homer of the year, eclipsing the nine he hit for the D-backs over 89 games in 2019.

Evan Longoria then doubled and scored on a big two-out single by rookie Joey Bart, who lined a 106.5 mph shot past Hosmer at first base to extend the Giants’ lead to 3-1. That brought up Yastrzemski, who delivered the biggest blow by sending a misplaced cutter from Paddack over the right-field wall and into the water for his second career Splash Hit.

Yastrzemski experienced tightness in his calf during a game against the Mariners last week, but the Giants decided not to place him on the 10-day injured list to preserve his chances of returning to play in the regular season. The 30-year-old slugger made steady progress in his rehab and cleared the final checkpoint after running the bases on Thursday. 

“It wasn't an ideal situation to go down in the timeframe that I did,” Yastrzemski said during a pregame Zoom call with reporters. “I wanted to get back as soon as possible, but at the same time, be smart about it because I want to be able to play for a few more weeks, not just a few more days.” 

Yastrzemski said he no longer feels discomfort in his calf when he’s in the batter’s box or when he runs, though he acknowledged that he will have to be judicious about when he pushes his body in the coming days. 

“I'm confident that I can just go out there and do what I need to do to try and help my team win at this point,” said Yastrzemski, who was in the starting lineup for Game 2 of the doubleheader. “Running is going to be situational. I'm not going to be busting it down the line when I hit a routine fly ball. But when it comes down to game-changing plays, I'm going to just have to give everything that I have in the tank right now.”