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.
Our Cardinals vs Cubs Pick
- Pick: St. Louis Cardinals +1.5
- Confidence: 3/5
Game Snapshot
- Matchup: St. Louis Cardinals vs Chicago Cubs
- Date & Time: Friday, September 26, 2025, 2:20 p.m. ET
- Starting Pitchers: Miles Mikolas (STL) vs Colin Rea (CHC)
- Stadium: Wrigley Field, Chicago, IL
- Broadcast: MLB Network
Key Storylines
Pitching matchup
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.
Key Players
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.
Recent team streaks
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.
Best Player Props
| 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 |
Betting Trends & H2H
- The season series between these teams is tied 5-5 heading into this series opener.
- The home team has won three of the last four games between these teams.
- St. Louis is 34-44 on the road for the season.
- Chicago is 47-31 at home on the year.
Cardinals vs Cubs Model Projection
Score Projection: Cardinals 4 – Cubs 5
Win Probability: Cardinals 36%, Cubs 64%
Final Thoughts
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.
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- Source: https://ats.io/mlb/st-louis-cardinals-vs-chicago-cubs-prediction-9-26-2025/468585/