MLB picks today: Tuesday's MLB best bets include Guardians vs. Red Sox play [9/22/2026]

Guardians vs. Red Sox Over 6.5 runs (-115)

• Edge: 7.8%
• Probability: 61.3%
• Matchup: Guardians vs. Red Sox (6:45PM ET)

Our model has identified value on Over 6.5 runs in Guardians vs. Red Sox at 53¢ odds. A 61.3% probability produces an edge of 7.8%, making this the strongest play for today's MLB slate.

Blue Jays vs. Orioles Over 7.5 runs (-108)

• Edge: 7.5%
• Probability: 59.4%
• Matchup: Blue Jays vs. Orioles (6:35PM ET)

Blue Jays vs. Orioles over 7.5 runs carries a 7.5% edge and a probability of 59.4% at 52¢ odds, according to our model.

Marlins vs. Cubs Over 6.5 runs (-112)

• Edge: 6.7%
• Probability: 59.5%
• Matchup: Marlins vs. Cubs (7:40PM ET)

Marlins vs. Cubs Over 6.5 runs at -112 odds shows a 6.7% edge, supported by a 59.5% probability in simulations.

Brewers vs. Phillies over 7.5 runs (+117)

• Edge: 6.2%
• Probability: 52.3%
• Matchup: Brewers vs. Phillies (6:40PM ET)

A 6.2% edge and 52.3% probability make Brewers vs. Phillies over 7.5 runs a value play in the Brewers vs. Phillies matchup, per our model.

Diamondbacks vs. Rockies Over 11 runs (+100)

• Edge: 6.1%
• Probability: 56.1%
• Matchup: Diamondbacks vs. Rockies (8:40PM ET)

Diamondbacks vs. Rockies Over 11 runs at +100 presents a 6.1% edge, with simulations resulting in a probability of 56.1%.

Twins vs. Giants Over 7.5 runs (+100)

• Edge: 5.6%
• Probability: 55.6%
• Matchup: Twins vs. Giants (9:45PM ET)

Our model finds value on Over 7.5 runs in Twins vs. Giants at 50¢, supported by an edge of 5.6%.

Cardinals vs. Pirates Over 7.5 runs (+117)

• Edge: 4.9%
• Probability: 51%
• Matchup: Cardinals vs. Pirates (6:40PM ET)

Our model has uncovered value on Cardinals vs. Pirates Over 7.5 runs at 46¢. A 51% probability produces a 4.9% edge, making this a strong play for today's MLB action.

Astros vs. Mariners Over 7.5 runs (+100)

• Edge: 4.9%
• Probability: 54.9%
• Matchup: Astros vs. Mariners (9:40PM ET)

A 4.9% edge on a 54.9% probability makes Over 7.5 runs at 50¢a solid value play in today's Astros vs. Mariners matchup.

Reds vs. BravesOver 9.5 runs (+113)

• Edge: 4.9%
• Probability: 51.8%
• Matchup: Reds vs. Braves (7:15PM ET)

Our model projects value on Over 9.5 runs at 47¢. A 51.8% probability produces a 4.9% edge, making the Over the favorable side in today's matchup.

Mets vs. Rangers Over 7.5 runs (-113)

• Edge: 4.5%
• Probability: 57.6%
• Matchup: Mets vs. Rangers (8:05PM ET)

Rounding out our top 10 bets, Mets vs. Rangers Over 7.5 runs at 53¢ shows a 57.6% probability and a 4.5% edge.

MLB best bets summary: Tuesday, 9/22/2026

As of 4:03AM ET, here are our top MLB bets by edge recommended by our model:

List of upcoming MLB games to bet on [9/22/2026]

• Blue Jays vs. Orioles (6:35PM ET, Tuesday)
• Cardinals vs. Pirates (6:40PM ET, Tuesday)
• Nationals vs. Tigers (6:40PM ET, Tuesday)
• Brewers vs. Phillies (6:40PM ET, Tuesday)
• Guardians vs. Red Sox (6:45PM ET, Tuesday)
• Reds vs. Braves (7:15PM ET, Tuesday)
• White Sox vs. Royals (7:40PM ET, Tuesday)
• Marlins vs. Cubs (7:40PM ET, Tuesday)
• Mets vs. Rangers (8:05PM ET, Tuesday)
• D-Backs vs. Rockies (8:40PM ET, Tuesday)
• Astros vs. Mariners (9:40PM ET, Tuesday)
• Angels vs. Athletics (9:40PM ET, Tuesday)
• Twins vs. Giants (9:45PM ET, Tuesday)
• Padres vs. Dodgers (10:10PM ET, Tuesday)

Conclusion

Our MLB best bets are locked and loaded for September 22, 2026, featuring plays such as over 6.5 runs in the Guardians vs. Red Sox matchup and over 7.5 runs in the Blue Jays vs. Orioles matchup. Powered by advanced simulations, these picks are here to boost your betting game.

Our predictions are sourced from current data to help you make informed decisions. For additional resources and advice, head to our Responsible Gambling hub.

All odds and probabilities in this article are correct and accurate at the time of publication.