The Boston Red Sox (55%) are favored to put an end to the Cleveland Guardians' winning streak tonight, and my Guardians vs. Red Sox predictions believe Boston profiles better on offense and in the bullpen.
Read on for my MLB picks for Tuesday, Sept. 22.
Who will win Guardians vs Red Sox today: Red Sox moneyline
For help understanding probabilities, see our odds calculator.
I’m on the Boston Red Sox up to 56%.
Payton Tolle ranks first among all of today’s projected starters in xFIP and SIERA over the past 30 days.
He's in elite form, and Red Sox relievers have suppressed hard contact more effectively than every other bullpen in September. Their pitching should be excellent from start to finish.
Isolating Parker Messick’s three most-used pitches, three of Boston’s projected Top-4 batters own xwOBAs of .390 or higher against southpaws this season.
The pitching should be great for both teams, but I have more trust in the top of Boston’s order to produce.
COVERS INTEL: Payton Tolle ranks in the 93rd percentile in xBA, and will make it hard on a Cleveland offense that sits 28th in average vs. left-handed pitching.
Guardians vs Red Sox Over/Under pick: Under 6.5
Scoring runs should be like pulling teeth for both sides, making the Under an appealing play to 52%.
Messick owns a remarkably strong 1.79 ERA through 13 starts in pitcher-friendly conditions. He conceded two runs or fewer in 11 of them.
Tolle’s xERA sits at 2.38 over 11 starts in favorable pitching weather. The Cleveland Guardians rank 27th in xwOBA vs. lefties the past month and are an unlikely candidate to knock Tolle off his game.
This has 4-2 written all over it. Give me the Under.
Guardians vs Red Sox home run prediction: Wilyer Abreu
Wilyer Abreu has been a consistent source of production against left-handed pitching.
His ISO sits at .190 facing southpaws but spikes to .267 when isolating the fastball-sinker combination that Messick relies on so heavily.
His strikeout rate sits at just 13.2% against those two pitches, which is below his barrel rate of 14.5%. It’s always a good sign when you’re making elite contact more frequently than punching out.
These are tough conditions to leave the park, but Abreu has the power to do it.
- ML/RL picks: 120-99, -2.29 units
- Over/Under picks: 113-100-6, -0.59 units
Guardians vs Red Sox weather
Poor hitting weather is expected with temperatures in the mid 50s and winds blowing in.
Guardians vs Red Sox odds
- Moneyline: Guardians 47% | Red Sox 54%
- Run line: Guardians +1.5 (66%) | Red Sox -1.5 (35%)
- Over/Under: Over 6.5 (53%) | Under 6.5 (48%)
Guardians vs Red Sox trend
Boston has hit the Under in 13 of its last 15 games (+10.90 units, 66%). Find more MLB betting trends for Guardians vs. Red Sox.
How to watch Guardians vs Red Sox and game info
| Location | Fenway Park, Boston, Mass. |
| Date | Tuesday, Sept. 22, 2026 |
| First pitch | 6:45 p.m. ET |
| TV | Guardians.TV, NESN |
| Guardians starting pitcher | Parker Messick (12-9, 2.57 ERA) |
| Red Sox starting pitcher | Payton Tolle (9-6, 3.02 ERA) |
Guardians vs Red Sox latest injuries
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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