Red Sox vs Guardians Prediction, Odds, Moneyline, Spread & Over/Under for Sept. 22

Odds updated as of 1:11 a.m.

In MLB action on Tuesday, the Boston Red Sox play the Cleveland Guardians.

Before you do any MLB betting on this game at FanDuel Sportsbook, here's what you need to know.

Red Sox vs Guardians Game Info

• Boston Red Sox (84-72) vs. Cleveland Guardians (81-75)
• Date: Tuesday, September 22, 2026
• Time: 6:45 p.m. ET
• Venue: Fenway Park -- Boston, Massachusetts
• Coverage: NESN and CleGuardians.TV

Red Sox vs Guardians Odds & Moneyline

• All MLB odds, betting lines and prop bets are available on FanDuel Sportsbook.
• Moneyline: BOS: (-130) | CLE: (+110)
• Spread: BOS: -1.5 (+168) | CLE: +1.5 (-205)
• Total: 6.5 -- Over: (-130) | Under: (+106)

Red Sox vs Guardians Probable Starting Pitchers

Probable Pitchers: Payton Tolle (Red Sox) - 9-6, 3.02 ERA vs Parker Messick (Guardians) - 12-9, 2.57 ERA

The probable starters are Payton Tolle (9-6) for the Red Sox and Parker Messick (12-9) for the Guardians. Tolle and his team are 10-14-0 ATS this season when he starts. When Tolle starts a game and his team is the favorite on the moneyline, they have a record of 12-5. The Guardians have a 16-14-0 ATS record in Messick's 30 starts with a set spread. The Guardians have a 5-1 record in Messick's six starts this season when they were the underdog on the moneyline.

Red Sox vs Guardians Prediction & Pick

All MLB win probability predictions and picks are according to numberFire.
Prediction: Red Sox win (59.1%)

Red Sox vs Guardians Moneyline

• Cleveland is the underdog, +110 on the moneyline, while Boston is a -130 favorite at home.

Red Sox vs Guardians Spread

• The Red Sox are 1.5-run home favorites on the runline against the Guardians. The Red Sox are +168 to cover, and the Guardians are -205.

Red Sox vs Guardians Over/Under

• A combined run total of 6.5 has been set for Red Sox-Guardians on Sept. 22, with the over at -130 and the under at +106.

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Red Sox vs Guardians Betting Trends

• The Red Sox have been chosen as favorites in 106 games this year and have walked away with the win 58 times (54.7%) in those games.
• This season Boston has been victorious 36 times in 67 chances when named as a favorite of at least -130 on the moneyline.
• The Red Sox and their opponents have hit the over in 68 of their 153 games with a total set by oddsmakers this season.
• The Red Sox have an against the spread mark of 72-81-0 in 153 games with a line this season.
• The Guardians have put together a 28-27 record in games they were listed as the moneyline underdog (winning 50.9% of those games).
• Cleveland has a 19-14 record (winning 57.6% of its games) when playing as a moneyline underdog of +110 or longer.
• The Guardians have played in 147 games with an over/under set, and have combined with opponents to go over the total 73 times (73-74-0).
• The Guardians have covered 47.6% of their games this season, going 70-77-0 against the spread.

Red Sox Player Leaders

• Wilyer Abreu is batting .251 with 36 doubles, four triples, 24 home runs and 70 walks. He has an on-base percentage of .332 while slugging .453.
• Among all qualifying hitters in MLB, his batting average ranks 77th, his on-base percentage ranks 67th, and he is 44th in slugging.
• Caleb Durbin is hitting .255 with 25 doubles, a triple, 13 home runs and 49 walks, while slugging .389 with an on-base percentage of .338.
• Among qualified hitters, his batting average places him 72nd, his on-base percentage 57th, and his slugging percentage 100th.
• Durbin has picked up at least one hit in three games in a row. In his last five games he is batting .375 with two doubles and three walks.
• Willson Contreras has 123 hits and an OBP of .387, both of which lead the Red Sox this season.
• Contreras heads into this game with two games in a row with at least one hit. In his last five games he is hitting .267 with a home run, two walks and two RBIs.
• Jarren Duran has 20 home runs, 69 RBI and a batting average of .204 this season.

Guardians Player Leaders

• Chase DeLauter has totaled 138 hits, a team-best for the Guardians. He's batting .291 and slugging .457 with an on-base percentage of .364.
• Including all qualifying hitters in MLB, he ranks 11th in batting average, 23rd in on-base percentage and 39th in slugging percentage.
• DeLauter heads into this game on a three-game hitting streak. In his last five games he is hitting .278 with a home run, four walks and three RBIs.
• Steven Kwan's .378 on-base percentage and .345 slugging percentage are both team-highs. He has a batting average of .280.
• He is 23rd in batting average, 10th in on-base percentage and 129th in slugging percentage in the majors.
• Jose Ramirez has 27 doubles, 12 home runs and 58 walks while hitting .237.
• Brayan Rocchio is hitting .250 with 24 doubles, two triples, 13 home runs and 37 walks.

Red Sox vs Guardians Head to Head

• 5/31/2026: 9-4 BOS (Favorite: Guardians, Spread: -1.5, Total: 7, Favorite Moneyline: -116, Underdog Moneyline: -102)
• 5/30/2026: 9-1 BOS (Favorite: Guardians, Spread: -1.5, Total: 6.5, Favorite Moneyline: -130, Underdog Moneyline: +110)
• 5/29/2026: 4-3 CLE (Favorite: Guardians, Spread: -1.5, Total: 8, Favorite Moneyline: -124, Underdog Moneyline: +106)
• 9/3/2025: 8-1 CLE (Favorite: Red Sox, Spread: -1.5, Total: 9, Favorite Moneyline: -154, Underdog Moneyline: +130)
• 9/2/2025: 11-7 BOS (Favorite: Red Sox, Spread: -1.5, Total: 7.5, Favorite Moneyline: -270, Underdog Moneyline: +220)
• 9/1/2025: 6-4 BOS (Favorite: Red Sox, Spread: -1.5, Total: 8, Favorite Moneyline: -144, Underdog Moneyline: +122)
• 4/27/2025: 13-3 BOS (Favorite: Red Sox, Spread: -1.5, Total: 7.5, Favorite Moneyline: -118, Underdog Moneyline: -100)
• 4/26/2025: 7-3 BOS (Favorite: Red Sox, Spread: -1.5, Total: 7.5, Favorite Moneyline: -116, Underdog Moneyline: -102)
• 4/26/2025: 5-4 CLE (Favorite: Red Sox, Spread: -1.5, Total: 7.5, Favorite Moneyline: -110, Underdog Moneyline: -106)
• 4/25/2024: 6-4 CLE (Favorite: Guardians, Spread: -1.5, Total: 7.5, Favorite Moneyline: -132, Underdog Moneyline: +112)

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