The iconic Route 66 rivalry returns to Wrigley Field this Independence Day, with the Cardinals (47–40) visiting the NL Central-leading Cubs (50–35) in the opener of this pivotal three-game series. With Miles Mikolas set to oppose Colin Rea in the starting pitching matchup, what’s the best bet in today’s Cardinals vs. Cubs matchup?
Cardinals vs. Cubs Game Info
St. Louis Cardinals at Chicago Cubs
2:20 p.m. ET, Friday, July 4, 2025
Wrigley Field, Chicago, IL
Cardinals vs. Cubs Public Betting & Odds
According to oddsmakers from online sportsbook Bovada.lv, the Cubs are -148 moneyline favorites to beat the Cardinals, who are +126 underdogs. The total, meanwhile, sits at 10.5 runs.
As of this writing, our MLB Public Betting data page shows that the majority of public bettors are on St. Louis.
Pitching Matchup & Odds
St. Louis sends veteran RHP Miles Mikolas (4–5, ~4.76 ERA) to the mound.
Chicago counters with RHP Colin Rea (5–3, 4.37 ERA).
The Cubs are strong favorites at –210 moneyline, while St. Louis sits at +172, with the O/U pegged at 8 runs.
Team Profiles
Cardinals:
St. Louis ranks ninth in MLB with 4.6 runs/game and boasts a disciplined lineup with a .327 OBP. Their rotation, anchored by sharpshooter Matthew Liberatore and ace Sonny Gray, is supported by the league’s top defense in Outs Above Average. Injuries have struck—catchers Ivan Herrera (hamstring) and Willson Contreras (hand, X‑rays negative) are questionable—but the lineup remains potent. Brendan Donovan (.308 AVG, 140 wRC+) and Nolan Arenado (10 HR) anchor the offense.
Cubs:
Chicago leads the league with 5.4 runs per game, powered by power bats like Kyle Tucker, Seiya Suzuki, and Pete Crow‑Armstrong. Their pitching staff holds a solid 3.84 ERA with Beckett standout Jameson Taillon (7–4, 3.84 ERA) among their top starters. Catcher Carson Kelly—formerly of St. Louis—hit for the cycle in late March and is settling in well behind the plate. The Cubs also feature one of baseball’s best bullpens and rank in the top 13 in WHIP.
Why It Matters
With absolute date clarity: it’s July 4, 2025, the first of three matchups during this series. These games could swing momentum in the NL Central, with the Cubs holding a narrow edge in the standings . Not to mention the emotional weight of rivalry, amplified by Wrigley Field on a holiday weekend.
Cardinals vs. Cubs Betting Prediction
Expect a tightly contested battle on Friday night, with both offenses capable of big innings, but pitching and situational hitting likely to decide the outcome. If Ley lineups grind out runs and leverage relief arms, the under eight total runs could hit. On the flip side, a breakout night from Suzuki or Tucker may tip the game in Chicago’s favor. For added drama, keep an eye on Contreras’s status and bullpen usage late in the game.
Cardinals vs. Cubs MLB PREDICTION: OVER 10.5