Minnesota Twins vs Cleveland Guardians Prediction 9/21/25 MLB Picks Today

The Cleveland Guardians and the Minnesota Twins meet Sunday in MLB action from Target Field. We will look at this from a betting perspective and determine the best bets for this game. Here’s a Cleveland Guardians vs. Minnesota Twins prediction.

Starting Pitching Matchup

The Cleveland Guardians will send out Joey Cantillo for the start here and Cantillo is 5-3 with a 3.27 ERA and 95 strikeouts this season. In his career, Cantillo is 0-2 with a 4.60 ERA and 17 strikeouts against Minnesota. The Minnesota Twins will send out Simeon Woods Richardson here and Woods Richardson is 7-4 with a 4.31 ERA and 95 strikeouts this season. In his career, Woods Richardson is 0-1 with a 2.49 ERA and 19 strikeouts against the Guardians.

Cleveland Guardians Recap

The Cleveland Guardians come into this game looking to add on to their double-header sweep of the Twins from Saturday, winning game one 6-0 before an 8-0 win in game two to improve to 84-71 this season. After this series, the Guardians will head home for what’s become a massive series against the Detroit Tigers.

Guardians Win Streak Now In Double-Digits

Steven Kwan has 159 hits as part of a .272 batting average and 10 home runs, 27 doubles and 49 RBIs. Kyle Manzardo has 104 hits with 17 doubles, 2 triples, 26 home runs and 67 RBIs as well this year. Gabriel Arias has 22 doubles but also 146 strikeouts and Manzardo has 123 strikeouts so far this season. Arias has also added 11 home runs and 50 RBIs and Jose Ramirez has chipped in 29 home runs and 80 RBIs with 39 stolen bases as well. 

Why the Cleveland Guardians will win

• The Guardians have won each of their last 10 games.
• The Twins have lost each of their last 11 games against the Guardians following a home loss.
• The Twins have failed to cover the run line in each of their last 11 home games against the Guardians following a home loss.
• The Guardians have covered the run line in each of their last nine road games.

Cleveland Guardians Player Prop Facts

• Jose Ramirez has hit a home run in each of the Guardians’ last two day games.
• Will Brennan has recorded at least one Double in each of his last three appearances with the Guardians as favorites against AL opponents.
• Lane Thomas has recorded at least one hit in each of his 12 previous road appearances against AL Central opponents that held a losing record.
• Jose Ramirez ranks 3rd in the league in Steals (40) this season.

Minnesota Twins Recap

The Minnesota Twins come into this game looking to salvage something here after the two losses on Saturday dropped them to 66-89 this season. After this series, the Minnesota Twins will head on the road for a set against the Texas Rangers.

Twins Drop 9 Of Last 11

Byron Buxton has 119 hits along with 18 doubles, a team-high 31 home runs and 76 RBIs with 22 stolen bases and 7 triples while Trevor Larnach’s chipped in 119 hits with 21 doubles, 16 home runs and 58 RBIs as well this season. Brooks Lee has contributed 105 hits with 14 doubles, 14 home runs and 58 RBIs and Matt Wallner has 22 homers and 40 RBIs as well. 

Why the Minnesota Twins will win

• The underdogs have won nine of the Guardians’ last 13 games at Target Field.
• The Guardians have lost three of their last four Sunday games as favorites.
• The Guardians have failed to cover the run line in each of their last eight Sunday games against AL Central opponents.
• The underdogs have covered the run line in 17 of the last 19 games between the Guardians and Twins.

Minnesota Twins Player Prop Facts

• Byron Buxton has hit at least one home run in each of his last five Sunday day appearances against teams that held a winning record.
• Ryan Jeffers has recorded at least one hit in each of his last six appearances in day games against teams that held a winning record.
• Byron Buxton ranks 7th amongst qualified players for Slugging Percentage (.540) this season.

Total Runs Facts

• Ten of the Guardians’ last 11 games after playing the previous day have gone UNDER the total runs line.
• Four of the Twins’ last five day games against American League opponents have gone UNDER the total runs line.

Cleveland Guardians vs. Minnesota Twins Prediction

I’m on the Guardians here. I just think that the Guardians, this is what they do. They play strong baseball in September and always give themselves a shot at the playoffs and the division. It’s in this team’s DNA. The Twins just look like they’ve given up and if you need proof of that, just look at the results from Saturday’s double-header. I’ll roll with Cleveland for the sweep here.