San Francisco Giants vs St. Louis Cardinals – MLB Preview – Sep 22, 2025

The St. Louis Cardinals head west to open a three-game series with the San Francisco Giants at Oracle Park. First pitch is set for 9:45 PM ET on Monday night. Both teams sit below .500 but remain in the wild-card conversation with only a week left in the regular season.
San Francisco enters 77-79 and three games behind the Reds and Mets for the final National League wild-card slot. St. Louis is 76-80, sitting one game further back. With the Reds and Mets idle Monday, neither team can be eliminated, but this series will likely decide which club stays alive heading into the weekend.
Giants Preview – Verlander Looks to Lead at Home
Justin Verlander gets the start for San Francisco. The 42-year-old righty has a 3-10 record with a 3.75 ERA across 22 starts. While wins have been scarce, his ERA and WHIP (1.29) remain competitive, giving the Giants a veteran presence on the mound.
Verlander saw these Cardinals earlier this month, working six shutout innings in a 3-2 loss on Sep 6. He is 3-1 with a 4.00 ERA in his career against St. Louis across six starts. His ability to keep the ball in the yard will be key after surrendering 17 home runs this season.
The Giants’ bullpen has been steady most of the year with a 3.64 ERA, though recent outings have been shaky. San Francisco dropped seven of eight before beating the Dodgers on Sunday, a result that manager Bob Melvin called a “huge game” to keep his team’s hopes alive.
Offensively, the Giants average 4.32 runs per game while allowing 4.23. They have been one of the league’s strongest Under teams at 73-76 O/U, and their home games often trend low-scoring. Still, they will need run support to back Verlander, as the lineup has struggled for consistency in September.
Cardinals Preview – McGreevy Gets Another Chance
Michael McGreevy will take the ball for St. Louis. The 24-year-old right-hander is 7-3 with a 4.08 ERA this year. He’s been up and down lately, throwing seven shutout innings against Cincinnati in his last start but giving up six runs in four innings to the Giants on Sep 5.
McGreevy has faced San Francisco twice, going 1-1 with a 5.25 ERA in 12 innings. His command will be critical, as he has allowed 17 walks over his past six outings. Keeping the Giants off the basepaths early is key to giving the Cardinals a chance on the road.
At the plate, the Cardinals are scoring 4.28 runs per game while allowing 4.59. The team has lost eight of its last 12 games, but they did finish their homestand with a 5-1 win over Milwaukee. Nolan Arenado’s status remains a storyline after his standing ovation Sunday, sparking speculation about his future with the franchise.
The bullpen has been inconsistent but has a few bright spots. JoJo Romero (2.14 ERA) and Matt Svanson (2.05 ERA) continue to anchor late innings. Injuries to key players like Willson Contreras and Masyn Winn have forced younger players into larger roles, making the final stretch more about development while still trying to chase wins.
Head-to-Head and Trends
The Cardinals won two of three when the teams met in St. Louis earlier this month. They are 7-3 in the last 10 meetings overall. San Francisco, however, is 38-37 at home this season, while St. Louis has struggled on the road with a 32-43 record.
Totals lean slightly to the Over when these teams meet. In their last 10 head-to-head matchups, seven games have gone Over the number. However, both clubs rank among the top half of the league in hitting the 1st 5 Innings Team Total Under trend, showing how slow starts have been common.
Betting Prediction
Current odds list San Francisco -155 on the moneyline, with St. Louis +125. The run line sits at Giants -1.5 (+150) and Cardinals +1.5 (-185). The total is set at 8 runs, shaded slightly to the Under at -125.
The Covers Score Predictor projects a tight game with San Francisco edging St. Louis 4.5 to 4.3, landing just over the posted total. The key matchup is Verlander versus McGreevy, as Verlander has proven steadier and has already handled this lineup recently.
Both teams are clinging to playoff hopes, but the Giants’ home advantage and veteran starter make the difference. St. Louis has been better in head-to-head play, but inconsistency on the road is hard to overlook. Final projection: Giants 5, Cardinals 4. That makes San Francisco the play on the moneyline with a slight lean to the Over.
Pick: Giants -155 (Moneyline), Over 8