Chicago Cubs vs Pittsburgh Pirates Prediction, Odds and Picks for Today, 09/16/25

The Cubs and Pirates play the 2nd game of a series on Tuesday night after the Cubs took the opener by a score of 4-0. That score is another regular reminder that the Pirates are the lowest scoring team in the league this season, and that you never really go wrong betting against this team scoring. The Cubs, on the other hand, continue to close in on a postseason berth, even as their own offense has cooled considerably down the stretch. Tuesday, of course, is also a Skenes day, which means the Pirates are installed as the favorite. But I am happy to fade that and take the overall better team. My Cubs vs Pirates pick is the Cubs on the money line at plus-money odds.

Skenes is incredible, no doubt about it. He has now gone over the 200K mark, and he sports an ERA below 2.00 and a WHIP below 1.00. The Cy Young looks like a certainty. On the other hand, the Pirates aren’t wild about running up his usage in a meaningless season either, so the Cubs likely only have to wait him out for 5 or 6 innings. Cade Horton is having a great campaign of his own, and he is the NL Rookie of the Year frontrunner. He has allowed a scant 5 runs over his last 10 starts combined (which is, by the way, well ahead of Skenes in that same stretch). If we get any kind of similar effort out of Horton, then I don’t see any reason we wouldn’t think the Cubs would pull this one out in the late innings. And it would just be one more reason for people to post all those graphics they love about Skenes getting no run support. Give me the Cubs.

Cubs vs Pirates prediction: Cubs ML (+110) available at time of publishing. Playable at that number.

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