St. Louis Cardinals vs Chicago Cubs Prediction - 9/26/2025
Updated September 25, 2025
Updated September 25, 2025
The St. Louis Cardinals and Chicago Cubs will face off in the first game of a three-game series on Friday afternoon. This series opener pits a rebuilding squad against a postseason hopeful in an NL Central contest with playoff implications for Chicago. The Cubs are 89–70 and looking to seal up the top Wild Card spot in the National League. Before the action begins at Wrigley Field, continue reading to get my Cardinals vs Cubs prediction.
Miles Mikolas draws the start for St. Louis today. Mikolas is 8–10 this season with an ERA of 4.76. He has had mixed results on the road and the Cardinals are hoping he can provide length and keep the Cubs’ offense in check. The Cubs will go with Colin Rea on the bump today. Rea enters at 10–7 with a 4.10 ERA and has been more reliable at home. I give the pitching edge to the Cubs by a slim margin here.
From St. Louis, Brendan Donovan has been turning heads, hitting .378 over his last 10 games, with multiple doubles, a homer, and a few walks. Ivan Herrera has powered some offense over that stretch as well. However, the Cardinals will miss Willson Contreras, who is on the injured list with a right shoulder strain.
For Chicago, Seiya Suzuki is always dangerous, and the Cubs’ offense has enough firepower to punish mistakes. Chicago has scored five runs or more in three straight games and will look for another offensive outburst today.
The Cubs have been struggling recently. They snapped a five-game losing streak with a 10–3 win over the Mets on Wednesday. But they lost to the Mets again on Thursday and Chicago is not heading in the right direction entering playoff time. The Cardinals had a three-game winning streak snapped in their loss to the San Francisco Giants yesterday.
Player | Prop Type | Projection |
|---|---|---|
Seiya Suzuki | Home Runs | Over 0.5 |
Brendan Donovan | Total Bases | Over 1.5 |
Colin Rea | Strikeouts | Over 5.5 |
Miles Mikolas | Strikeouts | Under 4.5 |
Score Projection: Cardinals 4 – Cubs 5
Win Probability: Cardinals 36%, Cubs 64%
I do think that the Cubs will win this game at home and potentially lock up the top Wild Card spot in the National League by the end of the night. But I also think that the Cardinals will cover the runline as an underdog in this game. St. Louis should be able to take advantage of the inconsistencies of Rea to make this a respectable game from Wrigley.
Jay Sanin is the GM and Head of Sports at ATS.io. He has been writing about sports gambling since 2013, handicapping tens of thousands of sporting events. He plays sides and totals aggressively across most sports and is more selective in player prop markets. He does his own modeling across most sports, and his family is jealous of how much time he spends on his precious spreadsheets.
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