The Chicago Cubs are a win away from clinching home-field advantage for their upcoming Wild Card series, while the St. Louis Cardinals are three games away from calling 2025 a season.
My Cardinals vs. Cubs predictions and MLB picks are calling for Chicago to take care of business in the series opener at Wrigley Field on Friday, September 26.
Cardinals vs Cubs prediction
Cardinals vs Cubs best bet: Cubs -1.5 (+110)
The Chicago Cubs have the pitching edge in Friday’s series opener, home-field advantage for their upcoming Wild Card series against the San Diego Padres is still up for grabs, and star outfielder Kyle Tucker (calf) could return to action this afternoon.
It all adds up to me siding with the motivated Chicago club over the St. Louis Cardinals at Wrigley Field in the series opener.
Cards righty Miles Mikolas has struggled to the tune of a 4.76 ERA, 1.33 WHIP, and 4.85 xFIP this season, and he allowed eight runs across just six innings in his lone 2025 start against the Cubbies.
While it isn’t all sunshine, lollipops, and rainbows for Chicago righty Colin Rea, either, the Cards offense hasn’t impressed offensively all season. St. Louis ranks 24th in wOBA and 28th in ISO against righties for the campaign, and sport respective 23rd-ranked and 30th-ranked overall marks in September.
As a result, even with Rea sporting a run-of-the-mill 4.10 ERA, 1.28 WHIP, and 4.40 xFIP, I’m confident he can navigate the St. Louis lineup well enough for the Chicago bats to do the heavy lifting to cover the number this afternoon.
Cardinals vs Cubs same-game parlay (SGP)
As discussed, the Cards are limping into this series offensively, and I’m not anticipating the Cubs racking up runs, either.
Both teams have long-standing trends to the Under, and they both played last night, so this is a quick turnaround for an afternoon tilt at Wrigley.
Alec Burleson sports a nine-game hitting streak and has posted a high-end .299 batting average against right-handed pitchers for the campaign.
Cardinals vs Cubs 3-leg SGP
- Cubs -1.5
- Under 9
- Alec Burleson Over 0.5 hits
Cardinals vs Cubs odds
- Moneyline: St. Louis +140 | Chicago -170
- Run line: St. Louis +1.5 | Chicago -1.5
- Over/Under: Over 8.5 | Under 8.5
Cardinals vs Cubs trend
The Cubs have hit the Under in 58 of their last 106 games (+13.15 Units / 11% ROI), and the Cardinals have played to the Under in 43 of their last 74 games (+7.70 Units / 9% ROI). Find more MLB betting trends for Cardinals vs. Cubs.
How to watch Cardinals vs Cubs and game info
| Location | Wrigley Field, Chicago, IL |
| Date | Friday, September 26, 2025 |
| First pitch | 2:20 p.m. ET |
| TV | FDSN-MW, MARQ |
| Cardinals starting pitcher | Miles Mikolas (8-10, 4.76 ERA) |
| Cubs starting pitcher | Colin Rea (10-7, 4.10 ERA) |
Cardinals vs Cubs latest injuries
Cardinals vs Cubs weather
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
Affiliate Disclosure: Our team of experts has thoroughly researched and handpicked each product that appears on our website. We may receive compensation if you sign up through our links.
