San Francisco Giants vs San Diego Padres Prediction, Preview and Odds - 08/21/2025

Game Time: 4:10 pm ET, Thursday, August 21, 2025

Venue:  Petco Park, San Diego, CA

Where to Watch:  NBCS-BA, PADRES.tv 

DraftKings:  Moneyline odds:  Giants +140, Padres -172; Over/Under:  8 runs

Bet365:  Moneyline odds:  Giants +145, Padres -175; Over/Under:  8 runs

BetMGM:  Moneyline odds:  Giants +145, Padres -175; Over/Under:  8 runs

San Francisco Giants:  61-65 (3rd place, NL West)

San Diego Padres:  70-56 (2nd place, NL West)

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San Francisco Giants:  2-8 last 10

San Diego Padres:  6-4 last 10

The Giants are entering this series off a win and lost their 3-game series against the Tampa Bay Rays 2-1 in their last series. They enter this game with a 61-65 record overall and have a road record of 31-32. This is the series finale of a 4-game series with the Padres on Thursday with the 3rd game still to be played on Wednesday. The Giants won the series opener on Monday and lost the 2nd game on Tuesday. Their offense ranks 26th in the MLB with a .684 OPS. Landen Roupp is their starting pitcher on Wednesday while Justin Verlander is making his start in this game on Thursday. He is 1-9 with a 4.23 ERA this season. His team lost their last 4 straight games this season with him making an appearance. In his last MLB regular season start, he allowed 0 ER, 0 HR, and 0 BB with 8 SO on 2 hits through 7 IP against the Tampa Bay Rays.

The Padres are entering this series off a loss and got swept in their 3-game series against the Los Angeles Dodgers 3-0 in their last series. They enter this game with a 70-56 record overall and have a home record of 39-21. This is the 4th game of a 4-game series with the Giants on Thursday with the 3rd game of this series still to be played on Wednesday. The Padres lost the 1st game of this series on Monday and won the 2nd game on Tuesday. Their offense ranks 22nd in the MLB with a .704 OPS. JP Sears is their starting pitcher on Wednesday while Dylan Cease is making his start in this game on Thursday. He is 5-11 with a 4.61 ERA this season. His team won 3 of their last 4 games this season with him making an appearance. In his last MLB regular season start, he allowed 3 earned runs, 0 homers, and 6 walks with 2 strikeouts on 2 hits through 3.1 innings pitched against the Los Angeles Dodgers.

The current betting odds have the Padres listed as a favorite in this game according to Draftkings Sportsbook. The Padres have looked really good in their games this season with their 70-56 record overall which has them right near the top of the NL West. They have looked great in their own ballpark too with their 39-21 home record this season. Meanwhile, the Giants haven't looked great in their games this season with their 61-65 record overall which has them right in the middle of the NL West. They haven't been a great road team either with their 31-32 road record. The Giants have also been in a big slump lately as they are 2-8 in their last 10 games while the Padres are 6-4 in their last 10. The Padres are going with Cease in this one and he hasn't looked great this season. He is 5-11 with a 4.61 ERA and has been giving up quite a few runs this year, but lately he has looked better. He did give up 3 earned runs in his last start, but he has been better lately and the team has been finding success with him too, winning 3 of their last 4 games with him starting. The Giants are also going with Verlander in this one and he hasn't looked good this year. He is 1-9 with a 4.23 ERA and the team has had almost no success with him this year. He is coming off a good start in which he gave up no runs, but that hasn't been a common theme for him this season and his team has still lost 4 games in a row now with him starting. The Giants have also struggled on the road all season and are in the middle of a huge slump while the Padres have looked good since the All-Star break and have been a different team in their ballpark. The best way to place a bet here is on the Padres to win this game. 

Giants Padres Prediction:  Our MLB Pick for Thursday, August 21, 2025 (4:10 pm ET start time) is Padres 7 Giants 3.

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San Francisco Giants: 221-229 (-35.8 units) on the moneyline in all games. 104-120 (-11.6 units) on the moneyline in road games. 161-164 (-20.7 units) on the moneyline against right-handed starters. 76-47 OVER as a road underdog of +100 or higher.

San Diego Padres: 90-58 (+12.3 units) on the moneyline vs. an NL team with a slugging percentage of .400 or worse on the season. 40-32 (+7 units) on the moneyline vs. a team with a good bullpen whose ERA is 3.45 or better. 147-132 (+4 units) on the moneyline vs. a team with a good bullpen whose WHIP is 1.350 or better. 39-26 OVER at home against division opponents.

San Francisco Giants:  M. Chapman (3B) Ten Day IL - Hand. J. Encarnacion (RF) Ten Day IL - Hamstring. E. Miller (RP) Fifteen Day IL - Elbow. T. Murphy (C) Sixty Day IL - Back.

San Diego Padres:  J. Merrill (CF) Day To Day - Undisclosed. M. King (SP) Fifteen Day IL - Knee. J. Brito (RP) Sixty Day IL - Forearm. J. Musgrove (SP) Sixty Day IL - Elbow.

“He had better stuff than he did last time. It looked like he was in command. He gives up a run in the first, but we make an error. He got out of that jam. It looked like his stuff was better. He was getting ahead. He was getting different swings. And then obviously, he went out for the fourth and hit a couple of guys and it kind of got away from him a little bit.” - Bob Melvin after his team’s loss against the Padres in their game on Tuesday.

“He just pitched like Nick pitches, almost regardless. He threw a lot of quality strikes. I loved the fact that we get dinged right off the bat … nobody hung their head, especially Nick -- the guy on the mound that has the ball. You look up, and that’s the only run he gave up.” - Mike Shildt after his team’s win against the Giants in their game on Tuesday.

Jung Hoo Lee (L) CF

Heliot Ramos (R) LF

Rafael Devers (L) DH

Casey Schmitt (R) 3B

Dominic Smith (L) 1B

Christian Koss (R) SS

Patrick Bailey (S) C

Drew Gilbert (L) RF

Tyler Fitzgerald (R) 2B

Fernando Tatis Jr. (R) RF

Luis Arraez (L) 1B

Manny Machado (R) 3B

Ryan O'Hearn (L) DH

Xander Bogaerts (R) SS

Ramón Laureano (R) CF

Gavin Sheets (L) LF

Jose Iglesias (R) 2B

Elias Díaz (R) C

Batting Average:  Dominic Smith (.282)

Hits:  Heliot Ramos (128)

Home Runs:  Willy Adames (19)

RBI:  Wilmer Flores (63)

Stolen Bases:  Jung Hoo Lee (10)

Wins:  Logan Webb (11)

Saves:  Camilo Doval (15)

ERA:  Keaton Winn (0.00)

Batting Average:  Freddy Fermin (.318)

Hits:  Luis Arraez (142)

Home Runs:  Manny Machado (20)

RBI:  Manny Machado (73)

Stolen Bases:  Fernando Tatis (25)

Wins:  Nick Pivetta (13)

Saves:  Robert Suarez (33)

ERA:  Bradgley Rodriguez (0.00)

Managers:

San Francisco Giants: Bob Melvin (2nd season)

San Diego Padres: Mike Shildt (2nd season)