Minnesota Twins vs Cleveland Guardians Prediction, Preview and Odds - 07/22/2026

Game Time: 6:40 pm ET, Wednesday, July 22, 2026

Venue:  Progressive Field, Cleveland, OH

Where to Watch:  MLB TV

DraftKings:  Moneyline odds:  Twins +104, Guardians -126; Over/Under:  8 runs

Bet365:  Moneyline odds:  Twins +105, Guardians -125; Over/Under:  8 runs

BetMGM:  Moneyline odds:  Twins +105, Guardians -125; Over/Under:  8 runs

Minnesota Twins:  49-52 (3rd place, AL Central)

Cleveland Guardians:  53-48 (2nd place, AL Central)

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Minnesota Twins:  5-5 last 10

Cleveland Guardians:  6-4 last 10

The Twins are entering this series off a loss and lost their 3-game series against the Chicago Cubs 2-1 in their last series. They enter this game with a 49-52 record overall and have a road record of 23-27. This is the 3rd game of a 4-game series with the Guardians on Wednesday with the 2nd game still to be played on Tuesday. The Twins lost the series opener on Monday. Their offense ranks 9th in the MLB with a .735 OPS. Rookie pitcher Kendry Rojas is their starting pitcher on Tuesday while Bailey Ober is making his start in this game on Wednesday. He is 7-3 with a 4.32 ERA this season. His team lost 2 of their last 3 games this season with him making an appearance. In his last MLB regular season appearance, he allowed 2 ER, 0 HR, and 2 BB with 7 SO on 5 hits through 5.1 IP against the Chicago Cubs.

The Guardians are entering this series off a loss and lost their 3-game series against the Pittsburgh Pirates 2-1 in their last series. They enter this game with a 53-48 record overall and have a home record of 26-24. This is the 3rd game of a 4-game series with the Twins on Wednesday with the 2nd game of this series still to be played on Tuesday. The Guardians won the 1st game of this series on Monday. Their offense ranks 26th in the MLB with a .689 OPS. Parker Messick is their starting pitcher on Tuesday while Slade Cecconi is making his start in this game on Wednesday. He is 4-6 with a 4.55 ERA this season. His team won 2 of their last 3 games this season with him making an appearance. In his last MLB regular season start, he allowed 3 earned runs, 0 homers, and 1 walk with 4 strikeouts on 6 hits through 3.2 innings pitched against the Minnesota Twins.

The current betting odds have the Twins listed as a slight underdog in this game according to Draftkings Sportsbook. The Guardians have looked good in their games this season with their 53-48 record overall which has them right near the top of the AL Central. They have looked good in their own ballpark too with their 26-24 home record this season. Meanwhile, the Twins haven't looked good in their games this season with their 49-52 record overall which has them right in the middle of the AL Central. They haven't been a great road team either with their 23-27 road record this year. The Twins were rolling into the All-Star break and now they have lost a lot of that momentum, going 5-5 in their last 10 games, but they are still right in the race for the AL Central and will be looking to bounce back after a rough stretch coming out of the break. The Guardians are 6-4 in their last 10 games and have looked a lot better lately, but they aren't going to have one of their stronger starters in this game and the Twins do have an edge here offensively. The Guardians are going with Cecconi in this one and he hasn't looked great this season. He is 4-6 with a 4.55 ERA and he has been giving up quite a few runs all season. The team has had more success lately, winning 2 of their last 3 games with him starting, but he did give up 3 earned runs in his last start which has been a common theme for him. The Twins are going with Ober in this one and he hasn't looked great this season either. He is 7-3 with a 4.32 ERA, but lately he has looked a lot better. He only gave up 2 earned runs in his last start, something that has been becoming a common theme with him, and even though they have lost 2 of their last 3 games with him starting, the team has had a lot of success with him this year. Look for the Twins to take advantage of this pitching matchup with the better offense and keep themselves in the division race. The best way to place a bet here is on the Twins to win this game. 

Twins Guardians Prediction:  Our MLB Pick for Wednesday, July 22, 2026 (6:40 pm ET start time) is Twins 5 Guardians 4.

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Minnesota Twins: 201-224 (-45.8 units) on the moneyline in all games. 94-118 (-19.9 units) on the moneyline in road games. 63-69 (-12.4 units) on the moneyline against division opponents. 32-16 OVER in road games.

Cleveland Guardians: 238-199 (+35.7 units) on the moneyline in all games. 125-94 (+10.5 units) on the moneyline in home games. 86-53 (+27.8 units) on the moneyline against division opponents. 23-17 OVER as a home favorite of -110 or higher.

Minnesota Twins:  A. Banda (RP) Sixty Day IL - Lat. M. Abel (SP) Sixty Day IL - Elbow. C. Prielipp (SP) Fifteen Day IL - Finger. M. Raya (SP) Fifteen Day IL - Shoulder. G. Acton (RP) Sixty Day IL - Shoulder. C. Sands (RP) Fifteen Day IL - Forearm. D. Festa (SP) Sixty Day IL - Shoulder. P. Lopez (SP) Sixty Day IL - Elbow.

Cleveland Guardians:  T. Herrin (RP) Fifteen Day IL - Elbow. A. Martinez (LF) Ten Day IL - Foot. J. Ramirez (3B) Ten Day IL - Hand.

“We battled to get back to .500, and the last three days we just have not played well.” - Derek Shelton after his team’s loss against the Guardians in their game on Monday.  

“It's fun to see guys hit home runs. It’s the coolest feeling in the world, hitting a home run in the big leagues. To see our guys keep doing it, obviously we're getting good pitches to hit and we're not missing them. I think that's more telling than anything. I'm just really, really happy for them.” - Stephen Vogt after his team’s win against the Twins in their game on Monday. 

Trevor Larnach (L) LF

Byron Buxton (R) CF

Kody Clemens (L) 2B

Josh Bell (S) DH

Royce Lewis (R) 1B

Victor Caratini (S) C

Brooks Lee (S) 3B

Alan Roden (L) RF

Ryan Kreidler (R) SS

Steven Kwan (L) LF

Travis Bazzana (L) 2B

Chase DeLauter (L) RF

Brayan Rocchio (S) SS

Rhys Hoskins (R) DH

Daniel Schneemann (L) 3B

David Fry (R) 1B

Patrick Bailey (S) C

Petey Halpin (L) CF

Batting Average:  Gabriel Gonzalez (.500)

Hits:  Josh Bell (90)

Home Runs:  Byron Buxton (25)

RBI:  Josh Bell (60)

Stolen Bases:  Luke Keaschall (12)

Wins:  Taj Bradley (9)

Saves:  Yoendrys Gómez (11)

ERA:  Yoendrys Gómez (1.65)

Batting Average:  Chase DeLauter (.286)

Hits:  Brayan Rocchio (91)

Home Runs:  Angel Martínez (11)

RBI:  Chase DeLauter (50)

Stolen Bases:  José Ramírez (24)

Wins:  Gavin Williams (10)

Saves:  Cade Smith (28)

ERA:  Franco Aleman (1.80)

Managers:

Minnesota Twins: Derek Shelton (1st season)

Cleveland Guardians: Stephen Vogt (3rd season)