Guardians vs. Red Sox Prediction, MLB Picks for Tuesday, September 22

Guardians vs. Red Sox is set for first pitch at 6:45 p.m. ET on Tuesday, September 22, with the Red Sox having a 1.72x payout if they win, via PrizePicks.

The Guardians will try to hold on to their slim AL Central lead with SP Parker Messick (12-9, 2.57 ERA) on the mound. The Red Sox, who have already locked up a playoff spot, will counter with SP Payton Tolle (9-6, 3.02 ERA).

Below, we’ll break down our Guardians vs. Red Sox prediction and picks for Tuesday’s MLB game, including game winner, over/under, and key player picks for PrizePicks.

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Guardians vs. Red Sox Prediction, Winner Payout, Over/Under – Tuesday, September 22

The Guardians have won five games in a row to overtake the White Sox in the AL Central. Their pitching staff played a major role, allowing 3 or fewer runs in three of the last four games. Pitching has been a clear stretch strength, with a 3.90 xERA (seventh) and 1.26 WHIP (eighth), per FanGraphs.

The Red Sox have seen their lineup struggle as the playoffs approach. Over their last 15 games, they scored 4 or fewer runs 12 times. They are 20th in runs scored this season, despite being tied for 10th in wOBA (.318). Power is a problem, as they are tied for the sixth-fewest home runs.

Guardians vs. Red Sox Winner Payout, Over/Under – Tuesday, September 22

The Red Sox enter Tuesday’s game as a home favorite against the Guardians returning a 1.72x payout if they win outright, via PrizePicks.

Here are the full payouts for the Guardians vs. Red Sox game on PrizePicks — where you can make real money predictions on every MLB game!

Make your Guardians vs. Red Sox prediction on the over/under on PrizePicks.

PrizePicks data is live as of writing and is subject to change.

Guardians vs. Red Sox Prediction on Over/Under – Tuesday, September 22

Here are the key game stats and trends behind our Guardians vs. Red Sox prediction on the over/under for Tuesday, September 22.

• The Guardians are 81-75 despite their modest +2 run differential.
• Cleveland has underwhelmed at the plate, ranking 26th in runs scored, 27th in home runs, and 27th in wOBA (.307).
• Tolle has been excellent for the Red Sox, recording a 3.02 ERA that is supported by an even more impressive 2.65 xERA. He has limited hitters to a 34.7% hard-hit rate on his way to a 1.07 WHIP.
• The Guardians already have problems hitting home runs and facing Tolle likely won’t help matters. He allows just 0.9 HR/9.
• Messick has been just as good as Tolle, posting a 2.57 ERA and a 3.10 xERA. He has not allowed more than 3 runs in a start since June 29.
• These two teams also have excellent bullpens. The Red Sox's unit has a 3.09 ERA and a 1.18 WHIP, and the Guardians' bullpen has been nearly as good with a 3.55 ERA and 1.25 WHIP.

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Guardians vs. Red Sox Picks, Player Stats for PrizePicks: 9/22/26

Here are top Guardians vs. Red Sox picks to target on PrizePicks for Tuesday, September 22. Today's MLB picks for PrizePicks include OF Steven Kwan and C Adley Rutschman.

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Guardians OF Steven Kwan vs. Red Sox: 1.5 Hits+Runs+RBIs

• With Kwan only hitting 3 home runs for the season, he has just 31 RBIs despite playing 146 games.
• The veteran outfielder is not hitting the ball hard, posting a 0.4% barrel rate and a 10.0% hard-hit rate for the season. For his career, he has a 1.4% barrel rate and an 18.5% hard-hit rate.
• Left-handed pitchers have held Kwan to a .288 wOBA, compared to a .350 wOBA against righties.
• Tolle has a robust 32.4% strikeout rate at home, ahead of a 25.1% strikeout rate on the road.

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Red Sox C Adley Rutschman vs. Guardians: 5.5 Hitter Fantasy Score

• Since being acquired from the Orioles, Rutschman is only 19 for 107 (.192) with a .364 slugging percentage over 27 games.
• The 28-year-old has a .316 wOBA, putting him on pace to finish with a wOBA below .320 for the third straight season.
• Left-handed pitchers have limited Rutschman to a .264 wOBA and a .111 ISO this year — which sits behind his .342 wOBA and .214 ISO vs. righties.
• Messick has been lights out on the road, limiting teams to a 0.91 WHIP. He has allowed 2 or fewer earned runs in each of his last eight outings away from Cleveland.

Add Adley Rutschman to your PrizePicks lineup now!

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Tuesday’s matchup between the Guardians and Red Sox could be a low-scoring battle with Messick squaring off against Tolle. With strong pitching on the mound, Rutschman and Kwan might have quiet nights at the plate.

Don’t wait until the first pitch — make your Guardians vs. Red Sox picks on PrizePicks now and earn real money if you’re right.

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