St. Louis Cardinals vs Pittsburgh Pirates Picks and Prediction for Tuesday September 22 2026

The St. Louis Cardinals visit the Pittsburgh Pirates at PNC Park in Pittsburgh, Pennsylvania, on Tuesday, September 22, 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 Cardinals snapped a four-game losing streak with a 5-3 victory over Washington on Sunday, while the Pirates have won four straight after completing a three-game sweep of Kansas City. St. Louis has the advantage in the season series at 6-4, although Pittsburgh won two of three when these teams 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 Andre Pallante, who enters at 12-7 with a 3.70 ERA and 1.26 WHIP through 151 innings. He has allowed 143 hits and 11 home runs while recording 104 strikeouts against 47 walks. Pittsburgh counters with Jared Jones, who is 4-6 with a 4.17 ERA and 1.19 WHIP over 90.2 innings. He has surrendered 77 hits and 12 home runs while striking out 109 and walking 31. Pallante owns the advantage in ERA and has worked considerably more innings, while Jones has the better WHIP and a major strikeout advantage on a per-inning basis. The contrasting profiles create a relatively balanced starting matchup, with St. Louis bringing the steadier run prevention and Pittsburgh offering the greater swing-and-miss potential.

Cardinals Try to Build on a Much-Needed Victory

St. Louis enters Tuesday below .500 at 76-80 despite owning a winning 38-37 record on the road. The Cardinals finally stopped a four-game slide Sunday by beating Washington 5-3, but their recent stretch has otherwise been difficult. St. Louis lost 8-5 in 11 innings and 9-1 in the first two games against Washington after dropping consecutive games to San Francisco. The Cardinals are just 1-4 over their last five completed games, scoring 19 runs while surrendering 36.

St. Louis is batting .242 as a team with 704 runs, 1,277 hits and 161 home runs. The Cardinals carry a .315 on-base percentage and .382 slugging percentage. Their pitching staff has struggled to a 4.29 ERA and 1.36 WHIP while opponents are batting .254. St. Louis pitchers have accumulated 1,235 strikeouts against 544 walks.

The Cardinals' biggest opportunity Tuesday comes from the starting-pitching matchup. Their scheduled starter carries a 3.70 ERA and has allowed only 11 home runs across 151 innings, giving St. Louis a chance to stabilize a pitching staff that has struggled overall. The concern is everything surrounding that advantage. Pittsburgh owns superior offensive numbers in virtually every major category and enters with considerably better recent form. St. Louis may need another strong starting performance to avoid turning this into a matchup between bullpens and offenses, where the statistical advantage shifts toward the home team.

Pirates Carry a Four-Game Winning Streak Into the Series

Pittsburgh enters Tuesday at 79-77 and is trying to secure a winning season with only a handful of games remaining. The Pirates are playing their best baseball of the current stretch, winning four consecutive games after a 5-4 loss to Milwaukee. Pittsburgh answered that defeat by beating Milwaukee 7-4 before sweeping Kansas City by scores of 8-5, 6-5 and 4-3. The Pirates are 4-1 across their last five completed games and have scored at least four runs in every contest during that span.

The Pirates are batting .254 with 748 runs, 1,363 hits and 181 home runs. They own a .332 on-base percentage and .406 slugging percentage, giving Pittsburgh a clear advantage over St. Louis in each category. The Pirates also have slightly better pitching numbers, carrying a 4.19 ERA and 1.30 WHIP while holding opponents to a .238 batting average. Pittsburgh has recorded 1,429 strikeouts against 563 walks.

Pittsburgh's biggest advantage is that its edge is spread throughout the team rather than concentrated in one category. The Pirates have the better batting average, on-base percentage, slugging percentage, team ERA, WHIP and opponent batting average. They have also hit 20 more home runs and scored 44 more runs than St. Louis. Add a 42-36 home record and a four-game winning streak, and Pittsburgh enters with several paths to victory even if the starting-pitching matchup does not provide a decisive advantage.

St. Louis Cardinals vs Pittsburgh Pirates Picks and Prediction

Pick: Pittsburgh Pirates Moneyline

St. Louis has the better starting ERA and leads the season series 6-4, but nearly everything else points toward Pittsburgh. The Pirates have won four consecutive games, are 42-36 at PNC Park and hold advantages over the Cardinals in batting average, on-base percentage, slugging percentage, team ERA, WHIP and opponent batting average. Pittsburgh's scheduled starter also owns a 1.19 WHIP and has recorded 109 strikeouts in only 90.2 innings. With St. Louis winning just once in its last five games, Pittsburgh is the preferred moneyline side rather than asking the Pirates to cover a run line.

Pick: Over 8.5 or Lower

The starting pitchers are capable of keeping this controlled early, but the full-game numbers create more appeal on the over at 8.5 or lower. St. Louis owns a 4.29 team ERA and 1.36 WHIP, while Pittsburgh's staff carries a 4.19 ERA. The Cardinals have allowed 36 runs over their last five games, an average of 7.2 per contest, while the Pirates have scored 29 during the same five-game span. Pittsburgh has reached at least four runs in five straight games, and St. Louis has enough offensive production to contribute against a Pirates staff that has not been dominant overall. At 8.5 or lower, the over is the preferred total.

Final Picks: Pittsburgh Pirates Moneyline and Over 8.5 or Lower

This preview was completed on Monday, September 21, 2026. Starting pitchers, betting lines and other game information are subject to change before the game begins.