Cardinals vs. Pirates Prediction: Paul Skenes Looks to Close Out St. Louis Series in Style

The St. Louis Cardinals wrap up a series at PNC Park on Thursday afternoon, taking on a Pittsburgh Pirates team that has quietly caught fire down the stretch. First pitch is set for 12:35 p.m. ET in a getaway-day matinee that pits a fading Cardinals club against a Pirates squad still boasting the reigning NL Cy Young winner at the top of its rotation. St. Louis sits at 77-81 and has been eliminated from playoff contention for weeks, playing out the string in the final days of a disappointing season. Pittsburgh, at 80-78, has nothing to play for in the standings either, but pride and roster evaluation matter plenty in the season’s final week, and the Pirates have been playing their best baseball of the year at the right time.

Why Pittsburgh Is a Heavy Home Favorite

Oddsmakers have installed the Pirates as clear favorites for this finale, with moneyline pricing around -160 to -165 at home against a Cardinals price near +135 to +136. The run line has Pittsburgh at -1.5 (+140 to +150) while St. Louis sits at +1.5 (-170 to -182), and the total is set at 6.5 to 7 runs. You can track the full MLB odds board for this series, and that gap reflects both the pitching matchup and the two teams’ recent trajectories — Pittsburgh has won six of its last ten games and rides a strong recent stretch into this one, while St. Louis has dropped four of its last six and enters on a mixed run of form. The Cardinals have actually cashed as moneyline underdogs at a decent clip this season, but this particular pitching mismatch is a significant factor working against them today.

Thu, Sep 24 • 12:36 PM ET

Spread

Money

Total

St. Louis Cardinals

+1.5 (-165)

+140 (+140)

O 7 (-102)

Pittsburgh Pirates

-1.5 (+152)

-159 (-159)

U 6.5 (+112)

Paul Skenes Headlines a Lopsided Pitching Matchup

The biggest storyline here is obvious: Paul Skenes takes the mound for Pittsburgh looking for his 11th win of the season. The reigning NL Cy Young winner has a 10-11 record with a 3.91 ERA, a 1.13 WHIP and 192 strikeouts across 31 starts and 168 innings in 2026 — numbers that look pedestrian only relative to his own historic standard from a season ago, when he led all of baseball in ERA and won the award unanimously. Skenes’ strikeout rate remains elite at better than a strikeout per inning, and he’s shown he can carry a lineup on any given afternoon, evidenced by a run of three straight starts this month in which the Pirates won each time he took the ball. St. Louis counters with right-hander Kyle Leahy, who has been a solid back-of-the-rotation piece for the Cardinals in 2026, sitting at 10-5 with a 3.65 ERA, a 1.34 WHIP and 129 strikeouts over 29 starts. Leahy has picked up six quality starts this season and has gone five-plus innings in 20 of his 29 outings, giving St. Louis a reasonable floor even without a marquee arm.

Offensively, the Cardinals will lean on a lineup built around Jordan Walker, Alec Burleson and shortstop Masyn Winn, while rookie infielder JJ Wetherholt has settled into the leadoff spot. Pittsburgh’s attack has produced 750 runs on the season against 719 allowed, a modest positive run differential that lines up with a club playing better ball of late. The Pirates’ bullpen has also been a quiet strength, with closer Gregory Soto racking up 16 saves and setup man Mason Montgomery posting a sparkling 2.59 ERA in middle relief — a duo that gives Pittsburgh a real advantage in a close, late-inning spot if this one stays tight into the seventh or eighth.

Head-to-head, this NL Central-adjacent series has generally favored the home team in this stretch of games, and Pittsburgh took both of the previous two matchups in this set, including a 2-0 shutout behind Jared Jones just two days prior. St. Louis’ offense has struggled to generate consistent runs against Pittsburgh pitching in this series, managing only a handful of runs total across the previous two games, which adds another layer of concern for the Cardinals heading into a matchup against one of the National League’s most dominant strikeout artists.

Prediction and Best Bet

Skenes gives Pittsburgh a decisive edge on the mound, and the Pirates’ recent form backs up the market’s confidence in them as sizable home favorites. St. Louis’ lineup has had trouble scoring in this series, and Leahy — while capable — doesn’t offer the same shutdown upside working the other way. Expect Pittsburgh to close out the series with a comfortable, low-scoring win behind another strong outing from its ace.

• Prediction: Pirates 5, Cardinals 2
• Best Bet: Pirates on the run line (-1.5)

With Skenes on the mound and the Pirates’ bullpen humming, Pittsburgh should be able to comfortably cover the run line against a Cardinals club that has struggled to find offense in this series and is playing out a lost season with little urgency.