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Cardinals vs Cubs Prediction 9/28/2025 Today’s MLB Picks

Sep 27, 2025; Chicago, Illinois, USA; Chicago Cubs first baseman Michael Busch (29) rounds the bases after hitting a solo home run against the St. Louis Cardinals during the first inning at Wrigley Field. Mandatory Credit: Kamil Krzaczynski-Imagn Images

Sep 27, 2025; Chicago, Illinois, USA; Chicago Cubs first baseman Michael Busch (29) rounds the bases after hitting a solo home run against the St. Louis Cardinals during the first inning at Wrigley Field. Mandatory Credit: Kamil Krzaczynski-Imagn Images

St. Louis (78-83) vs Chicago (91-70)

September 28, 2025 at 03:20 PM EDT

The Line: Betting Odds: Chicago -175 — Over/Under: 8.5

(Get latest betting odds)

In this article we will formulate a Cardinals vs Cubs prediction for this MLB game on Sunday, September 28th at Wrigley Field in Chicago, Illinois. Let’s take a look at the prediction for this MLB matchup. 

St. Louis Cardinals Betting Preview

The St. Louis Cardinals are 78-83 this year after they lost the first two games in this series by scores of 1-12 and 3-7. In their game two loss, St. Louis cut the deficit to 4-3 in the seventh inning, but immediately allowed a run in the bottom half of the inning to seal the loss. The Cardinals recorded seven hits in the game and they were led by Walker, who went 1-2 with one home run and two RBIs in the loss. St. Louis started McGreevy, who allowed six hits and three earned runs over 4.2 innings for the loss, while Alcala and Fernandez both allowed two earned runs in relief. 

Prior to this series, the Cardinals won two out of three against the Giants and two out of three against the Brewers. St. Louis has lost three games in a row and they are fourth in the NL Central standings. The St. Louis pitching staff has a 4.30 ERA with a 1.33 WHIP and a .260 opponent batting average, while their offense has scored 689 runs with a .245 batting average and a .315 on base percentage this season. Wilson Contreras (IL) has led St. Louis with 20 home runs, 80 RBIs, and five stolen bases, while Alec Burleson has added 18 home runs and 69 RBIs this year. The projected starting pitcher for St. Louis is Kyle Leahy, who is 4-2 with a 3.18 ERA and a 1.26 WHIP over 85.0 innings pitched this year. 

Chicago Cubs Betting Preview

The Chicago Cubs are 91-70 this season after they won game two by a score of 7-3 on Saturday. Chicago was tied at one in the fourth inning, but they scored six of the last eight runs to pull away with the win. The Cubs recorded 10 hits in the game and they were led by Busch, who went 4-4 with two home runs and four RBIs in the win. Chicago started Taillon, who allowed three hits and one earned run over 6.0 innings for the win, while Thielbar allowed two earned runs in relief. 

Prior to this series, the Cubs lost two out of three against the Mets and all four against the Reds. Chicago has won three of their last four games and they are second in the NL Central standings. The Chicago pitching staff has a 3.82 ERA with a 1.18 WHIP and a .239 opponent batting average, while their offense has scored 791 runs with a .250 batting average and a .321 on base percentage this season. Seiya Suzuki has led Chicago with 31 home runs and 102 RBIs, while Pete Crow-Armstrong has added 31 home runs and 95 RBIs this year. The projected starting pitcher for Chicago is Javier Assad, who is 3-1 with a 4.26 ERA and a 1.29 WHIP over 31.2 innings pitched this season. 

Why the Cubs will beat the Cardinals 

The Cubs have won each of their last seven games against National League opponents that held a losing record.
The Cardinals have lost eight of their last nine games at Wrigley Field against NL Central opponents that held a winning record.
The Cubs have covered the run line in nine of their last 10 games against teams that held a losing record.
The Cardinals have failed to cover the run line in eight of their last nine games at Wrigley Field against NL Central opponents that held a winning record.
The Cubs have led after 5 innings in seven of their last eight day games against the Cardinals.
The Cardinals have lost the first inning in four of their last five games at Wrigley Field against opponents that held a winning record.
The Cubs have led after 3 innings in six of their last seven games at Wrigley Field against National League opponents that held a losing record.

Why the Cardinals will beat the Cubs 

The Cubs have lost eight of their last 10 day games at Wrigley Field following a home win.
The Cubs have failed to cover the run line in five of their last six home games against National League opponents following a home win.

Total Runs Facts

Eight of the Cubs’ last nine home games have gone OVER the total runs line.
Four of the Cardinals’ last five games have gone OVER the total runs line.
The ‘Inning 1 OVER 0.5 runs’ market has hit in each of the Cardinals’ last five day games at Wrigley Field.
The ‘Inning 1 OVER 0.5 runs’ market has hit in each of the last four day games between the Cardinals and Cubs.

Chicago Cubs Player Prop Facts

Seiya Suzuki has recorded at least one hit in each of his last eight home appearances.
Seiya Suzuki has hit a home run in four of the Cubs’ last five games against the Cardinals at Wrigley Field.

St. Louis Cardinals Player Prop Facts

Alec Burleson has hit a home run in five of his last 14 appearances against the Cubs after playing the previous day.
Brendan Donovan has recorded at least one Double in four of his last five appearances against NL opponents.
Brendan Donovan has recorded at least one hit in each of his last eight appearances against NL opponents.

Cardinals vs Cubs Prediction 

Chicago has dominated the first two games in this series and they have scored 19 runs so far in the series. The Cubs are 49-31 at home this season, while the Cardinals are 34-46 on the road. St. Louis is finishing another season below .500 and they are starting Leahy, who will be an opener. Chicago is going with Assad, who has allowed 2, 4, and 3 earned runs in his last three starts. The Cubs are smashing the baseball right now, but I don’t love Assad, so I will back the over here.

David Racey's Pick: Over 8.5

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