Milwaukee Brewers vs. San Diego Padres Prediction and Picks – September 23, 2025

The Brewers and Padres will meet for the second game of their 2025 San Diego series this Tuesday night, and we'll preview the lines and odds in our Milwaukee Brewers vs. San Diego Padres prediction. The Padres have dominated the series recently – their win in Monday's opener brought them up to 3-1 against the Brewers this season and 7-3 against them in their past ten meetings. Game 2 is set to start at 9:40 PM ET on Tuesday, September 23.

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Will Brewers stay atop the National League?

At 95-62, the Milwaukee Brewers boast the best record in Major League Baseball heading into the final week of the regular season. They've only five games left to play, and the only NL team within five games of their record is the 92-64 Philadelphia Phillies. Will the Brewers finish the season strong and lock up the top seed in the NL playoff bracket?

The Brewers' offense has been dominant this season – they enter Tuesday ranked third in runs (794), second in hits (1,392) and batting average (.260), and 11th in OPS (.740). They've been as good on defense, ranking second in ERA (3.61), third in batting average allowed (.230), and seventh in WHIP (1.23).

Bruce Zimmerman will start Tuesday's game for the Brewers. A relief pitcher, Brewer was promoted to the team's roster on Saturday after having last played at the MLB level in 2023. He's hard to project, but he doesn't figure to stay on the mound deep into the game.

Can Padres maintain dominance in series?

The San Diego Padres are 86-71, already locked into a playoff berth in 2025, and only 2.5 games behind the Dodgers for the lead in the NL West. They have five games left to play: two more against the Brewers and a home series against the Arizona Diamondbacks. Can they capitalize on their matchups against a Brewers team that they're 7-3 against in their last ten meetings, including Monday's 5-4 win?

The Padres rank 19th in runs (670), 12th in hits (1,325), 8th in batting average (.252), and 18th in OPS (.708) entering Tuesday. Defensively, they're third in team ERA (3.67) and WHIP (1.21), while allowing a league-low batting average to their opponents (.225).

Randy Vasquez will start for the Padres on Tuesday. He's posted a 3.94 ERA and 1.36 WHIP for the season, but has only posted a 5-7 record overall. His last start, on the road against the Mets, ended ingloriously – Vasquez left before the end of the third inning, and his earned run total immediately went up when Brandon Nimmo hit a three-run homer off of relief pitcher Wandy Peralta.

Milwaukee Brewers vs. San Diego Padres Pick

Spread Pick for Milwaukee Brewers vs. San Diego Padres

• San Diego Padres +1.5 (-182) (4 Units)

The Padres have hounded the Brewers in recent meetings, winning seven of their last ten. Of the remaining three games, only one – the Brewers' 6-2 win in June of 2024 – came by more than a single run. I'd take the Padres to keep things close at home, especially given a starting pitcher for the Brewers that probably won't overwhelm them.

Over/Under Pick for Milwaukee Brewers vs. San Diego Padres

• Over 8.5 (-115) (4 Stars)

There's a reasonable chance neither pitcher puts on a great show of keeping the score down; Zimmerman is years away from his last MLB pitch, and Vasquez had a day to forget in his last outing. Each of the last five games between the Brewers and Padres in San Diego has ended with them hitting the Team Total Over. I expect we'll get another wave of points on the board in this one.