Guardians vs. Twins Prediction, Odds, Picks - September 21

The Cleveland Guardians versus Minnesota Twins game on Sunday at 2:10 p.m. ET will feature a pair of hot hitters in Bo Naylor and Byron Buxton. The Guardians are favored in this one, at -142, while the underdog Twins have +119 odds to win. Cleveland is the run-line favorite (-1.5). An 8.5-run total is set for the contest.

Here's everything you need to know from a betting perspective on the Guardians-Twins game, regarding the run line, moneyline and total, plus expert picks.

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Guardians vs. Twins Game 1 Highlights | MLB on FOX

Check out the best moments between the Cleveland Guardians and Minnesota Twins.

Guardians vs. Twins Game Information & Odds

• When: Sunday, September 21, 2025 at 2:10 p.m. ET
• Where: Target Field in Minneapolis, Minnesota
• How to watch on TV: MNNT and CLEG

Guardians vs. Twins Prediction

• Score Prediction: Guardians 5, Twins 4
• Total Prediction: Over 8.5 runs
• Win Probabilities: Guardians 51%, Twins 49%

Guardians vs. Twins Betting Insights

• This season, the Guardians have been favored 66 times and won 42, or 63.6%, of those games.
• Cleveland is 13-5 this season when entering a game favored by -142 or more on the moneyline.
• The implied probability of a win from the Guardians, based on the moneyline, is 58.7%.
• The Twins have been underdogs in 64 games this season and have come away with the win 24 times (37.5%) in those contests.
• This year, Minnesota has won nine of 25 games when listed as at least +119 or worse on the moneyline.
• Oddsmakers have implied with the moneyline set for this matchup that the Twins have a 45.7% chance of pulling out a win.

Guardians Recent Betting Performance

• The Guardians won all of the six games they played while the moneyline favorite in their last 10 matchups.
• Over their last 10 outings, the Guardians and their opponents combined to hit the over on the run total one time (all 10 games had set totals).
• The Guardians have put together an 8-2-0 record against the spread over their past 10 games.

Guardians Recent Stats

Guardians Player Insights

• Jose Ramirez paces the Guardians in home runs (30), runs batted in (81) and has racked up a team-high batting average of .282.
• Of all hitters in the majors, Ramirez is 19th in home runs and 41st in RBI.
• Ramirez takes a hitting streak of four games into this matchup. During his last five outings he is hitting .294 with a double, two home runs, five walks and three RBIs.
• Steven Kwan is hitting .276 with 28 doubles, a triple, 10 home runs and 54 walks.
• Kwan is 206th in homers and 140th in RBI among all MLB hitters this season.
• Kwan enters this game looking for his fourth game in a row with a hit. During his last five outings he is hitting .318 with a double, two walks and five RBIs.
• Kyle Manzardo is hitting .235 with 17 doubles, two triples, 26 home runs and 48 walks.
• Angel Martinez is hitting .228 with 23 doubles, two triples, 11 home runs and 22 walks.

Guardians Team Props

Twins Recent Betting Performance

• The Twins have played as underdogs in six of their past 10 games and won one of those contests.
• The Twins and their opponents have combined to hit the over four times in their last 10 games with a total.
• The Twins have a record of 3-7-0 ATS over their last 10 games.

Twins Recent Stats

Twins Player Insights

• Buxton leads the Twins with 31 home runs and 76 runs batted in, while recording a team-best batting average of .266.
• Buxton's home run total puts him 15th in the majors, and he ranks 56th in RBI.
• Trevor Larnach is hitting .251 with 22 doubles, a triple, 17 home runs and 53 walks.
• Larnach is currently 108th in home runs and 118th in RBI in the big leagues.
• Brooks Lee is hitting .239 with 15 doubles, a triple, 15 home runs and 30 walks.
• Royce Lewis has 17 doubles, 12 home runs and 25 walks while batting .239.

Twins Team Props

Guardians vs. Twins Game 1 Highlights | MLB on FOX

Check out the best moments between the Cleveland Guardians and Minnesota Twins.

FOX Sports created this story using technology provided by Data Skrive and data from Sportradar.

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