Giants vs. Cardinals Prediction, Odds, Probable Pitchers, Prop Bets for Wednesday, Sept. 16

A three-game set between the San Francisco Giants and St. Louis Cardinals wraps up on Wednesday afternoon, one of four games that have a first pitch before 3:30 p.m. EST.

The Cardinals are an extreme long shot to make the playoffs, sitting 7.5 games out of the final wild card spot after dropping Tuesday night’s matchup. Meanwhile, the Giants have long been eliminated from the playoffs and are 26 games under .500 in 2026.

Oddsmakers have set the Cardinals as favorites at home on Wednesday, and it makes sense since San Francisco is 23 games under .500 on the road this season.

Still, the pitching matchup on Wednesday afternoon leaves a lot to be desired on both sides.

San Francisco has right-handed Anthony Molina on the mound for his fifth appearance with the team (fourth start) after he began the season with the Atlanta Braves. Molina (5.24 ERA) was rocked for seven runs and nine hits in his last outing.

He’ll take on Cardinals lefty Matthew Liberatore – a former top prospect – who has not put things together in 2026, posting a 5.53 ERA in 29 starts.

Here’s a breakdown of the odds, a player prop to bet and my prediction for this matinee matchup.

Giants vs. Cardinals Odds, Run Line and Total

Odds via DraftKings Sportsbook

Run Line

Giants +1.5 (-163)
Cardinals -1.5 (+134)

Moneyline

Giants: +138
Cardinals: -168

Total

8 (Over -110/Under -110)

Giants vs. Cardinals Probable Pitchers

San Francisco: Anthony Molina (3-1, 5.24 ERA)
St. Louis: Matthew Liberatore (5-14, 5.53 ERA)

Giants vs. Cardinals How to Watch

Date: Wednesday, Sept. 16
Time: 1:15 p.m. EST
Venue: Busch Stadium
How to Watch (TV): NBC Sports Bay Area, Cardinals.TV
Giants record: 63-89
Cardinals record: 75-77

Giants vs. Cardinals Best MLB Prop Bets

Cardinals Best MLB Prop Bet

Alec Burleson OVER 1.5 Hits Runs and RBIs (-154)

This season, Cardinals slugger Alec Burleson is hitting .285 with an .824 OPS, and he’s been red hot as of late, hitting .316 with an OPS over 1.000 over the last week.

Against right-handed pitching this season, Burleson is hitting .316 with a .942 OPS and 20 of his 23 home runs. So, he’s a threat to have a big game against Molina, who allowed nine hits in his last outing and has given up 23 hits in 22.1 innings this season.

Over the last week, Burleson has six hits, one homer, seven runs batted in and three runs scored in six games. He’s also picked up two or more hits, runs and RBIs in four of his last five games.

I think he’s a solid prop target at home against a shaky starting pitcher on Wednesday.

Giants vs. Cardinals Prediction and Pick

Both of these teams have posted rather middling offensive numbers in the 2026 season, ranking 18th (San Francisco) and 21st (St. Louis) in the league in Weighted Runs Created Plus (wRC+).

However, both of these pitchers have really struggled in the 2026 season, and I think eight runs is very reachable after these teams combined for 13 on Tuesday night.

The OVER has hit in over 52 percent of the Giants’ games overall and 53.6 percent of their road games in 2026.

With Molina and Liberatore on the mound, both offenses should find some success early in this game.

Molina was obviously rocked in his last outing, and he’s given up 12 runs in three starts with the Giants this season. Meanwhile, Liberatore ranks in the 12th percentile in expected ERA and the 14th percentile in expected BAA, allowing four or more runs in 15 of his 29 outings this season.

Both of these teams have bullpens with ERAs over 4.00 as well, so the scoring likely won’t stop once these starters exit. Plus, the fact that we can get a push at eight runs makes the OVER even more intriguing on Wednesday afternoon.

Pick: OVER 8 (-110 at DraftKings)

Odds refresh periodically and are subject to change.

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