St. Louis Cardinals vs Pittsburgh Pirates Picks and Prediction for Wednesday September 23 2026

The St. Louis Cardinals visit the Pittsburgh Pirates at PNC Park in Pittsburgh, Pennsylvania, on Wednesday, September 23, 2026. First pitch is scheduled for 6:40 PM ET with coverage on MLB.TV. St. Louis enters at 76-80 overall and 38-37 on the road, while Pittsburgh is 79-77 overall and 42-36 at home. The Pirates entered this series riding a four-game winning streak and sit third in the NL Central, three games ahead of the fourth-place Cardinals. St. Louis holds a 6-4 advantage in the completed season series entering this three-game set, although Pittsburgh won two of three when the clubs last met in late August. At the time of this writing the odds were not released. Be sure to check out our free MLB picks for more MLB predictions throughout the season.

Starting Pitchers

St. Louis is scheduled to start Matthew Liberatore, who enters at 5-14 with a 5.36 ERA and 1.49 WHIP through 149.1 innings. He has allowed 167 hits and 27 home runs while recording 148 strikeouts against 55 walks. Pittsburgh's starting pitcher remains undecided in the information available at the time of this preview. That uncertainty needs to be considered before wagering, but the confirmed side of the pitching matchup presents an opportunity for Pittsburgh. Liberatore has allowed more hits than innings pitched, carries a WHIP approaching 1.50 and has been vulnerable to the long ball. Until Pittsburgh announces its starter, the Cardinals' pitching matchup can be evaluated much more confidently than the Pirates' side.

St. Louis Needs to Reverse Its Recent Slide

St. Louis enters Wednesday at 76-80 overall and has actually been slightly better away from home, where the Cardinals are 38-37. Their recent results have been much less encouraging. St. Louis is just 1-4 over its five most recently completed games, with its lone victory coming 5-3 against Washington. The Cardinals lost the other four by scores of 8-5 in 11 innings, 9-1, 6-5 in 10 innings and 10-3. That works out to 19 runs scored and 36 allowed over the five-game stretch, with the pitching staff surrendering at least six runs in each of the four defeats.

The Cardinals are batting .242 with 704 runs, 1,277 hits and 161 home runs this season. They carry a .315 on-base percentage and .382 slugging percentage. The pitching staff has posted a 4.29 ERA and 1.36 WHIP while issuing 544 walks and recording 1,235 strikeouts. Opponents are batting .254 against St. Louis pitching. None of those numbers are disastrous individually, but nearly every major team category trails Pittsburgh's corresponding mark.

Run prevention is the primary concern for St. Louis entering this matchup. The Cardinals have allowed 36 runs over their last five games, and Wednesday's scheduled starter carries a 5.36 ERA, 1.49 WHIP and 27 home runs allowed. That is a difficult combination against a Pittsburgh offense that has produced more runs, hits and home runs than St. Louis this season. The Cardinals have played reasonably well on the road and hold the season-series advantage, but they need a major improvement from their pitching to turn those factors into a victory Wednesday.

Pittsburgh Looks to Maintain Its Offensive Momentum

Pittsburgh comes into Wednesday at 79-77 overall and has been considerably better at PNC Park, posting a 42-36 home record. The Pirates entered this series on a four-game winning streak and are 4-1 over their five most recently completed games. Pittsburgh beat Kansas City 8-5, 6-5 and 4-3 after defeating Milwaukee 7-4, with its only loss during that span coming 5-4 against Milwaukee. The Pirates scored 29 runs and allowed 22 over those five games, averaging 5.8 runs per contest.

The Pirates are batting .254 with 748 runs, 1,363 hits and 181 home runs. Their .332 on-base percentage and .406 slugging percentage are both better than St. Louis' marks. Pittsburgh's pitching staff owns a 4.19 ERA and 1.30 WHIP with 563 walks and 1,429 strikeouts while holding opponents to a .238 batting average. Compared with St. Louis, Pittsburgh has the advantage in batting average, runs, hits, home runs, OBP, slugging percentage, ERA, WHIP, strikeouts and opponent batting average.

Pittsburgh's biggest advantage is the way its offensive profile matches up with the confirmed St. Louis starter. The Pirates have 181 home runs compared with 161 for the Cardinals, and St. Louis' scheduled starter has surrendered 27 long balls over 149.1 innings. Pittsburgh is also reaching base at a .332 rate and has averaged nearly six runs per game over its last five contests. The unknown starting pitcher creates some uncertainty on the Pirates' side, but Pittsburgh's stronger offense, better recent form and home-field performance make it the more attractive team entering Wednesday.

St. Louis Cardinals vs Pittsburgh Pirates Picks and Prediction

Pick: Pittsburgh Pirates Moneyline

Pittsburgh is the preferred side, provided the eventual moneyline remains reasonable after its starting pitcher is announced. The Pirates have been better statistically across almost every major team category, including a .254 batting average compared with .242 for St. Louis, a .332 OBP compared with .315 and a .406 slugging percentage compared with .382. Pittsburgh is also 42-36 at home and entered the series having won four straight, while St. Louis went just 1-4 over its previous five completed games and allowed 36 runs during that stretch. The uncertainty surrounding Pittsburgh's starter prevents this from being an especially aggressive play before the pitching matchup is finalized, but the Pirates still have enough advantages elsewhere to get the moneyline lean.

Pick: Over 8.5 or Lower

The over is the stronger total angle if the eventual number opens at 8.5 or lower. St. Louis has allowed 36 runs over its last five completed games, including at least six runs in four of those contests, while Pittsburgh has scored 29 runs during its 4-1 stretch. The confirmed St. Louis starter enters with a 5.36 ERA and 1.49 WHIP and has surrendered 27 home runs, creating a favorable matchup for a Pittsburgh offense with 181 homers and a .406 slugging percentage. Pittsburgh's undecided starter introduces additional uncertainty rather than strengthening an under case. With both clubs capable of contributing offensively and St. Louis struggling to prevent runs, 8.5 or lower is the range where the over becomes attractive.

Final Picks: Pittsburgh Pirates Moneyline and Over 8.5 or Lower

This preview was completed on Tuesday, September 22, 2026. Starting pitchers, betting lines and other game information are subject to change before the game begins.