Cubs vs. Pirates prediction: Cy Young candidate Paul Skenes takes on Cubs tonight [9/16/2025]

MLB action continues on Tuesday at 6:40PM ET as the Chicago Cubs lock horns with the Pittsburgh Pirates at PNC Park.

Cy Young hopeful Paul Skenes (10-9, 1.92 ERA) will start for the Pirates, pitting him against Cade Horton (10-4, 2.70 ERA) for the Cubs.

Based on updated simulations, Dimers' advanced MLB model projects the Pirates as the most likely winner of today's game.

For expanded analysis of Tuesday's matchup, including best bets and picks, visit our interactive Cubs vs. Pirates predictions page.

Pirates vs. Cubs prediction: Who will win, cover the run line?

Using powerful machine learning and statistical analysis, we have simulated the result of Tuesday's MLB game between the Cubs and Pirates 10,000 times as part of our MLB predictions coverage.

Our famous predictive model currently gives the Pirates a 54% chance of beating the Cubs.

According to our model, the Cubs (+1.5) have a 65% chance of covering the run line, while the 6.5-run over/under has a 56% chance of going over.

Cubs vs. Pirates odds [9/16/2025]

We have researched the best MLB odds in America for this game, which are listed here:

Bet Type	Cubs	Pirates
Run Line	+1.5 (-220)	-1.5 (+180)
Moneyline	+110	+117
Total	o6.5 (-115)	u6.5 (-105)

All odds are correct at the time of publication and are subject to change.

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Cubs vs. Pirates picks and best bets

Our model's strongest edge in today's Cubs vs. Pirates matchup is on the moneyline.

Our expert predictions, matched against the latest odds, reveal the best MLB picks and MLB best bets for every game throughout the season.

Unlimited access to our full set of picks, including this one, is available via Dimers Pro.

Calling Our Shot's best bets

Calling Our Shot produces daily MLB betting content, including the predictions featured below.

Cubs vs. Pirates game-day updates and essential details

Tuesday's MLB game between the Pirates and Cubs at PNC Park is scheduled to start at 6:40PM ET.

• Who: Chicago Cubs vs. Pittsburgh Pirates
• Date: Tuesday, September 16, 2025
• Time: 6:40PM ET/3:40PM PT
• Venue: PNC Park

Dimers' full preview of Tuesday's Cubs vs. Pirates matchup includes our prediction, picks and the latest betting odds.

Before making any Cubs vs. Pirates picks, be sure to check out the latest MLB predictions and betting advice from Dimers Pro.

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Conclusion

We predict the Pirates, with a 54% win probability, will likely beat the Cubs on Tuesday.

AI and automation have enhanced this article to quickly deliver accurate Cubs vs. Pirates insights, with human oversight ensuring high editorial quality. Our predictions are sourced from the latest data to help you make informed decisions. For additional resources and advice on responsible gambling, please call 1-800-GAMBLER.

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