Cleveland Guardians vs Minnesota Twins Prediction, Preview and Odds - 05/21/2025

Game Time: 1:10 pm ET, Wednesday, May 21, 2025

Venue:  Target Field, Minneapolis, MN 

Where to Watch:  MLB Network

DraftKings:  Moneyline odds:  Guardians +120, Twins -142; Over/Under:  7.5 runs

Bet365:  Moneyline odds:  Guardians +120, Twins -140; Over/Under:  7.5 runs

BetMGM:  Moneyline odds:  Guardians +120, Twins -140; Over/Under:  7.5 runs

Cleveland Guardians:  25-21 (4th place, AL Central)

Minnesota Twins:  26-21 (2nd place, AL Central)

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Cleveland Guardians:  4-6 last 10

Minnesota Twins:  9-1 last 10

The Guardians are entering this series off a loss and got swept in their 3-game series against the Cincinnati Reds 3-0 in their last series. They enter this game with a 25-21 record overall and have a road record of 11-13. This is the series finale of a 3-game series with the Twins on Wednesday with the series opener and the 2nd game still to be played on Tuesday in a double-header after Monday’s game was rained out. Their offense ranks 21st in the MLB with a .687 OPS. Gavin Williams is their starting pitcher on Tuesday while Tanner Bibee is making his start in this game on Wednesday. He is 3-4 with a 4.06 ERA this season. His team lost their last 2 straight games this season with him making an appearance. In his last MLB regular season start, he allowed 4 ER, 2 HR, and 1 BB with 4 Ks on 10 hits through 6 IP against the Cincinnati Reds.

The Twins are entering this series off a loss and won their 3-game series against the Milwaukee Brewers 2-1 in their last series. They enter this game with a 26-21 record overall and have a home record of 15-6. This is the 3rd game of a 3-game series with the Guardians on Wednesday with the 1st game and the 2nd game still to be played on Tuesday after Monday’s game was rained out. Their offense ranks 19th in the MLB with a .696 OPS. Chris Paddack is their starting pitcher on Tuesday while Joe Ryan is making his start in this game on Wednesday. He is 4-2 with a 2.42 ERA this season. His team won their last 2 straight games this season with him making an appearance. In his last MLB regular season start, he allowed 0 earned runs, 0 homers, and 1 BB with 9 strikeouts on 2 hits through 6 innings played against the Milwaukee Brewers.

The current betting odds have the Twins listed as a favorite in this game according to Draftkings Sportsbook. The Twins have looked good in their games this season with their 26-21 record overall which has them in 2nd place of their division. They have also looked great in their own ballpark this year with their 15-6 home record. Meanwhile, the Guardians have looked good in their games this season with their 25-21 record overall, but that record has them near the bottom of the division. They aren't too many games away from the Twins in 2nd place, but the Guardians haven't been a great road team this year with their 11-13 road record. The Guardians have also been struggling a lot more lately as they are 4-6 in their last 10 games while the Twins have been getting really hot, going 9-1 in their last 10 games. The Twins also have the better pitching matchup here and they can take advantage of that. Bibee is on the mound for the Guardians and he is 3-4 with a 4.06 ERA this season, but he did give up 4 earned runs in his last start and the team has lost 2 games in a row now with him starting. Ryan has been the much more reliable starter this season as he is 4-2 with a 2.42 ERA and coming off a great start in which he gave up no runs. Ryan is going to have another good start here at home so look for the Twins to take advantage of this pitching matchup and stay hot. The best way to place a bet here is on the Twins to win this game. 

Guardians Twins Prediction:  Our MLB Pick for Wednesday, May 21, 2025 (1:10 pm ET start time) is Twins 4 Guardians 2.

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Cleveland Guardians: 139-125 (+6.2 units) on the moneyline against right-handed starters. 97-73 (+9.4 units) on the moneyline vs. a team slugging percentage .410 or worse on the season  (AL). 136-121 (+16.8 units) on the moneyline vs. a team with a good bullpen whose WHIP is 1.350 or better. 46-24 UNDER as an underdog of +125 to +175.

Minnesota Twins: 197-179 (-24.9 units) on the moneyline in all games. 107-80 (-8.9 units) on the moneyline in home games. 82-77 (-13.6 units) on the moneyline when the money line is -100 to -150. 23-15 UNDER revenging a loss vs opponent as a road favorite.

Cleveland Guardians:  B. Lively (SP) Fifteen Day IL - Forearm. P. Sewald (RP) Fifteen Day IL - Shoulder. S. Bieber (SP) Sixty Day IL - Elbow. E. Sabrowski (RP) Sixty Day IL - Elbow. L. Thomas (CF) Ten Day IL - Wrist. T. Stephan (RP) Sixty Day IL - Elbow. J. Means (SP) Sixty Day IL - Elbow. D. Fry (C) Sixty Day IL - Elbow. S. Hentges (RP) Sixty Day IL - Shoulder.

Minnesota Twins:  D. Coulombe (RP) Fifteen Day IL - Forearm. L. Keaschall (2B) Sixty Day IL - Forearm. B. Buxton (CF) Seven Day IL - Head. C. Correa (SS) Seven Day IL - Concussion. M. Tonkin (RP) Sixty Day IL - Shoulder. M. Wallner (RF) Ten Day IL - Hamstring.

“I know what it takes now to manage in the major leagues. I know what a full year looks like. But it’s a new year, so everything’s brand new again. Being able to look back at things from last year is going to be super helpful. But I think if you feel you’ve did it all right, it’s going to pass you by so I’m always going to continue to push and learn as much as I can. You’re always adapting in this game.” - Stephen Vogt on his goals for the Guardians this season. 

"There's a reason why this is the type of injury we have these types of protocols --many, many steps and clearances you have to go through. Because there's not an easy way to diagnose and treat and monitor. You have to be thoughtful." - Rocco Baldelli on the injury to Byron Buxton.

Steven Kwan (L) LF

Angel Martínez (S) 2B

José Ramírez (S) 3B

Kyle Manzardo (L) DH

Carlos Santana (S) 1B

Nolan Jones (L) CF

Gabriel Arias (R) SS

Bo Naylor (L) C

Will Brennan (L) RF

Ryan Jeffers (R) C

Brooks Lee (S) SS

Royce Lewis (R) DH

Ty France (R) 1B

Trevor Larnach (L) LF

Jonah Bride (R) 3B

Carson McCusker (R) RF

Harrison Bader (R) CF

Willi Castro (S) 2B

Batting Average:  Steven Kwan (.311)

Hits:  Steven Kwan (56)

Home Runs:  Kyle Manzardo (10)

RBI:  Kyle Manzardo (25)

Stolen Bases:  José Ramírez (12)

Wins:  Emmanuel Clase (4)

Saves:  Emmanuel Clase (9)

ERA:  Hunter Gaddis (1.00)

Batting Average:  Luke Keaschall (.368)

Hits:  Ty France (42)

Home Runs:  Byron Buxton (10)

RBI:  Byron Buxton (27)

Stolen Bases:  Byron Buxton (8)

Wins:  Pablo López (4)

Saves:  Jhoan Duran (8)

ERA:  Danny Coulombe (0.00)

Managers:

Cleveland Guardians: Stephen Vogt (2nd season)

Minnesota Twins: Rocco Baldelli (7th season)