MLB Picks Today: Predictions & Best Bets for September 22, 2026 | SharpSide

The 16-game MLB slate on Tuesday provides a full menu of wagering opportunities. Our model indicates significant disagreement with market consensus in several matchups, notably a 2.0-run side edge toward the San Diego Padres in Los Angeles and a 1.2-run total edge on the Twins-Giants game. We identify a 1.1-run side edge toward the Milwaukee Brewers in Philadelphia. Today's Best Bet is highlighted immediately after this lede. This brief refreshes at 11:30 am Eastern based on new analytics, weather factors, pitching changes, and line movement, so the featured matchups may update between this morning publish and that refresh.

Today's Best Bet: Arizona Diamondbacks ML

This is the single game and line SharpSide has the highest confidence in today. Our model projects the Arizona Diamondbacks to win by a clear 1.3 runs, with a final score of 6.1–4.8 against the Colorado Rockies. This margin is roughly in line with the market's implied margin. This pick represents a conviction play for SharpSide, rather than a significant edge against current pricing. We find the model's projected outcome to be one of the most reliable on the slate, signaling a comfortable win probability for the Diamondbacks. Best Bet: Arizona Diamondbacks ML (-192)

San Diego Padres @ Los Angeles Dodgers

The SharpSide model projects the San Diego Padres to defeat the Los Angeles Dodgers 4.7–4.3, a 0.4-run margin in favor of the Padres, while the market consensus favors the Dodgers 5.0–3.5, a 1.5-run margin. This creates a 2.0-run side differential more favorable to the San Diego Padres than the market suggests. Furthermore, the model projects a total of 9.0 runs compared to the posted O/U line of 8.5, indicating a +0.5-run betting line edge on the Over. On the mound for San Diego is Michael King, who enters with a 4.16 FIP and a 0.99 HR/9, indicating he limits home runs and performs better than his ERA suggests when accounting for defense. The Dodgers counter with a TBA starter, whose season stats are unavailable in this build, creating an unknown for the home team's pitching plans beyond the first few innings. King averages nearly six innings per start, providing durability for the Padres. The San Diego Padres bullpen has performed well this season with a 3.48 relief ERA, significantly better than the league average of 4.10, and carries a low fatigue index of 0.07. This strong relief corps causes a -0.28 run nudge to the Los Angeles Dodgers' projected runs. Conversely, the Los Angeles Dodgers bullpen holds a 3.87 relief ERA, which is above average, but carries a taxed fatigue index of 0.20, suggesting their high-leverage arms may be limited. The Padres enter this series opener in excellent form, going 9-1 in their last 10 games, while the Dodgers are 7-3. San Diego has been unlucky on balls in play, with a .286 BABIP (league average .290), leading the model to regress their offense up by +0.06 runs, pushing the side lean toward the Padres and the total up. The Dodgers, meanwhile, have been lucky with a .297 BABIP, resulting in a -0.11 run regression to their offense, which pulls the side away from the Dodgers and the total down. No notable park or weather conditions are expected to impact run scoring. How the model decided: The biggest factor favoring San Diego Padres is San Diego Padres's 3.48 bullpen ERA, a better-than-average run-prevention mark that also tops Los Angeles Dodgers's 3.87. Secondary support comes from Los Angeles Dodgers's fortunate 0.297 BABIP, worth a negative 0.11-run offensive regression against them. Lean: San Diego Padres ML (+101)

Minnesota Twins @ San Francisco Giants

The SharpSide model projects the San Francisco Giants to narrowly win 4.4–4.3 against the Minnesota Twins, while the market consensus favors the Twins 4.2–3.3. This represents a 1.0-run side shift more favorable to the San Francisco Giants than the market. Additionally, the model projects a total of 8.7 runs compared to the posted O/U line of 7.5, indicating a +1.2-run betting line edge on the Over. This also represents a +1.2-run gap versus consensus. The Twins send Taj Bradley to the mound, who has a 3.86 FIP and a 10.39 K/9 this season, demonstrating an ability to limit hard contact and generate swings-and-misses. For the Giants, Anthony Molina, with a 3.35 FIP and 0.96 HR/9, shows strong underlying metrics despite his ERA, but he has a modest 28.0 IP this season and averages a short 4.67 IP per start, meaning the Giants' bullpen will be heavily exposed. The Minnesota Twins bullpen has a 4.83 relief ERA, well above the league average, and carries a fatigue index of 0.15, causing a +0.52 run nudge to the San Francisco Giants' projected runs. The San Francisco Giants bullpen has a 4.21 relief ERA, also slightly above average, and has a 0.15 fatigue index, contributing a +0.25 run nudge to the Minnesota Twins' projected runs. The Giants are also missing core hitter Jung Hoo Lee, which docks their projection by approximately 0.09 runs. Weather conditions are expected to add 0.22 runs to the projected total, a material factor. In terms of recent form, both teams are struggling, with the Twins 4-6 and the Giants 3-7 in their last 10 games. The Twins have been unlucky on balls in play with a .285 BABIP, leading the model to regress their offense up by +0.07 runs, pushing the side lean toward the Twins and the total up. The Giants have neutral BABIP luck. How the model decided: The biggest factor favoring San Francisco Giants is Minnesota Twins's vulnerable 4.83 bullpen ERA, worse than the roughly 4.10 league average, which improves San Francisco Giants's scoring outlook late. Supporting it: San Francisco Giants's starter carrying a 3.35 FIP, better than league average and stronger than the opposing starter's 3.86. At +112 the market prices San Francisco Giants near 47% while the model has them around 52%, so a meaningful share of this lean is price value rather than fundamentals. Lean: San Francisco Giants ML (+112)

Milwaukee Brewers @ Philadelphia Phillies

The SharpSide model projects the Milwaukee Brewers to win 4.3–4.1 against the Philadelphia Phillies, a 0.2-run margin in favor of the Brewers. In contrast, the market consensus favors the Phillies 4.2–3.3, a 0.9-run margin. This results in a 1.1-run side differential more favorable to the Milwaukee Brewers than the market suggests. Additionally, the model projects a total of 8.4 runs compared to the posted O/U line of 7.5, indicating a +0.9-run betting line edge on the Over. Dustin May takes the mound for the Milwaukee Brewers, with a 3.50 FIP and a 0.77 HR/9, showcasing excellent control over contact quality and home run suppression. However, May averages only 4.43 innings per start, indicating a short outing and exposing the Brewers' bullpen earlier than a typical starter. Facing him for the Philadelphia Phillies is Zack Wheeler, who has a 3.47 FIP and an impressive 10.60 K/9, suggesting he is a dominant force on the mound. Wheeler averages 5.61 IP per start. The Milwaukee Brewers bullpen has a strong 3.41 relief ERA and a very low fatigue index of 0.00, causing a -0.41 run nudge to the Philadelphia Phillies' projected runs. This solid relief corps is crucial given May's projected short outing. The Philadelphia Phillies bullpen, with a 4.34 relief ERA, is below average, and carries a negative fatigue index of -0.13, causing a -0.16 run nudge to the Milwaukee Brewers' projected runs. The Brewers enter this series opener in strong form, with an 8-2 record in their last 10 games, while the Phillies are 4-6. The Brewers have been lucky on balls in play, with a .315 BABIP, leading the model to subtract a significant -0.42 runs from their offense. The Phillies have been unlucky with a .283 BABIP, resulting in a +0.10 run regression to their offense. Weather conditions are immaterial for run impact. How the model decided: The biggest factor favoring Milwaukee Brewers is Milwaukee Brewers's 3.41 bullpen ERA, a better-than-average run-prevention mark that also tops Philadelphia Phillies's 4.34. Supporting it: Milwaukee Brewers's starter running a 0.77 HR/9, better-than-average home-run suppression and lower than the opposing starter's 1.20. At +116 the market prices Milwaukee Brewers near 46% while the model has them around 50%, so a meaningful share of this lean is price value rather than fundamentals. Lean: Milwaukee Brewers ML (+116)

First Five Innings: Toronto Blue Jays @ Baltimore Orioles (F5 OVER)

The F5 total for the Toronto Blue Jays @ Baltimore Orioles game presents a +1.05-run edge for the Over, with our model projecting 4.95 runs compared to the market-implied 3.90. This projection is anchored by the starters: Max Scherzer for the Blue Jays, whose blended F5 ERA is 5.90, and Chris Bassitt for the Orioles, with a blended F5 ERA of 4.52. Both offenses also show a slight upward regression for balls in play, with Toronto's .287 BABIP pushing their offense up by +0.07 runs, and Baltimore's .288 BABIP adding +0.06 runs. The park factor in Baltimore is 0.930, slightly dampening offense, but not enough to offset the pitching and offensive context. Lean: F5 OVER 4.0 total

How the model decided

Today's largest divergences from market consensus are driven by a combination of starting pitcher analytics, offensive BABIP regression, and bullpen effectiveness. The San Diego Padres' lean is heavily influenced by their strong bullpen and the Dodgers' taxed relievers, coupled with Padres' offensive regression from an unlucky BABIP. For the Minnesota Twins @ San Francisco Giants matchup, the material impact of weather and the Twins' below-average bullpen are key factors. In the Milwaukee Brewers @ Philadelphia Phillies game, Dustin May's strong FIP, despite a shorter outing, combined with the Brewers' elite and well-rested bullpen, provided a significant boost to their projected win probability. The model also considered advanced Sabermetric data, systems trends, and other analytics.

How to read this

This analysis reflects the SharpSide model's view of value compared to current market pricing and should not be considered financial advice. Odds and lines are subject to change.

Projections update after publish. This brief is locked in at the 11:30 am ET refresh, but the model keeps recalculating all day as lineups are posted, weather shifts, pitching changes are announced, and lines move — a side or total highlighted here can flip before first pitch. Always confirm the current number on the live projections page (which locks 30 minutes before each game's first pitch) before placing a bet.