St. Louis Cardinals vs Chicago Cubs Picks & Predictions for Sunday, September 28, 2025

By: Kim Smith Published 09/28/2025, 12:20 AM ET

The St. Louis Cardinals (79-79, 3rd in NL Central) face the Chicago Cubs (89-69, 2nd in NL Central) in the final game of a three-game series at Wrigley Field, with the Cubs aiming to solidify their playoff seeding and the Cardinals looking to end the season on a high note. Chicago’s potent offense and St. Louis’s inconsistent pitching create a favorable setup for run-scoring. Our free MLB picks leverage advanced metrics to pinpoint the best betting opportunities in this NL Central rivalry clash.

Game Setup

  • Date: September 28, 2025
  • Location: Wrigley Field, Chicago, Illinois
  • Time: 3:20 PM EDT
  • TV: Bally Sports Midwest (Cardinals broadcast), Marquee Sports Network (Cubs broadcast)
  • Weather: 60°F, partly cloudy, 8-12 mph winds blowing in from left field—slightly favoring pitchers.

Advanced Metrics Comparison

Offense

Metric St. Louis Cardinals Chicago Cubs Batting Average .246 .251 OPS .720 .745 wRC+ 95 (estimated, below league average) 105 (estimated, above league average) Run Differential -20 +65

The Cubs’ offense ranks top-10, led by Michael Busch (.256 AVG, 30 HR, 82 RBI) and Ian Happ (.246 AVG, 28 HR), with 211 homers (6th in MLB). The Cardinals, paced by Nolan Arenado (.268 AVG, 22 HR) and Willson Contreras (.261 AVG, 18 HR), struggle with consistency (615 runs, 22nd), hindered by a .405 SLG (20th).

Defense/Pitching

Metric St. Louis Cardinals Chicago Cubs ERA 4.25 3.90 WHIP 1.30 1.25 FIP 4.10 (estimated) 3.85 (estimated) Bullpen Usage High (4.20 ERA, taxed by short starts) Moderate (3.64 ERA, 42 saves, rested)

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Chicago’s pitching staff excels, with a top-10 ERA and low walk rate (400 BB, 5th in MLB). Their bullpen (3.64 ERA) ranks among the league’s best. St. Louis’s pitching (4.25 ERA, 18th) and bullpen (4.20 ERA) struggle, especially on the road, allowing a .265 OBA. Injuries to Steven Matz (elbow) and JoJo Romero (forearm) further strain their relief corps.

Efficiency Metrics

The Cubs’ high strikeout rate (8.4 K/9) and low walks (400 BB) reflect efficiency, with a FIP (3.85) indicating sustainable pitching strength. The Cardinals’ 8.0 K/9 and higher walk rate (420 BB) expose control issues, particularly against power-heavy lineups like Chicago’s. No direct PFF/PER equivalent, but the Cubs’ WAR leaders (Busch, Hoerner) outshine St. Louis’s (Arenado, Gorman).

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Situational Breakdown

  • Home vs. Away Performance: Cubs are 47-30 at home, with a +40 run differential at Wrigley. Cardinals are 36-42 on the road, with a -25 run differential, struggling to contain offenses away from Busch Stadium.
  • Day/Night Game Records: Day game (3:20 PM EDT). Cubs are 32-24 in day games, leveraging their offense (.260 AVG). Cardinals are 28-30 in day games, with a 4.40 ERA in afternoon contests.
  • First Five Innings vs. Full Game: Cubs’ starters (3.75 ERA) dominate early, while Cardinals’ starters (4.10 ERA) falter. Chicago’s bullpen (3.64 ERA) outshines St. Louis’s (4.20 ERA), giving the Cubs a full-game edge.

Market Odds & Projections

  • Moneyline: Cubs -155 (61%), Cardinals +130 (43%)
  • Run Line: Cubs -1.5 (+120, ~45%), Cardinals +1.5 (-140, ~58%)
  • Total: Over 8.5 (-110, ~52%), Under 8.5 (-110, ~52%)
  • Projection Models/Simulations: ESPN Analytics gives the Cubs a 57% win probability. Dimers simulations (10,000 runs) project a 58% win chance for Chicago, with an average score of 5-3. FanGraphs models favor the Cubs in ~56% of sims, with the over hitting in 55% of scenarios.

Picks For Cardinals vs Cubs

  1. Cubs Moneyline (-155): Chicago’s superior offense (.745 OPS, 105 wRC+) and pitching (3.90 ERA, 1.25 WHIP) overpower St. Louis’s weaker road performance (36-42, 4.40 ERA). Thompson’s 3.62 ERA and 2-0 record vs. the Cardinals in 2025 outmatch Pallante’s 4.32 ERA, supported by the Cubs’ 47-30 home record.
  2. Over 8.5 Total Runs (-110): Wrigley’s hitter-friendly conditions, St. Louis’s shaky pitching (4.25 ERA, 1.30 WHIP), and the Cubs’ power (211 HR) drive scoring. Pallante’s 4.32 ERA and Chicago’s .450 SLG at home, combined with 4 of 6 head-to-heads in 2025 clearing 8 runs, back the over.
  3. Cubs First Five Innings -0.5 (+110): Thompson’s early dominance (2.90 ERA in first 5 IP) and the Cubs’ strong home F5 splits (4.2 runs/game) outmatch Pallante’s road struggles (4.80 ERA). St. Louis’s .240 AVG in early innings on the road makes this a value bet.
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