Yankees vs Guardians Prediction, Picks and MLB Prop Bets for April 21: Take NY to Cover

Two of the four American League teams with the best winning percentage will play the series opener on Monday when Clarke Schmidt is set to pitch for the New York Yankees. Gavin Williams is expected to get the call for the Cleveland Guardians.

The Yankees are listed by MLB betting odds as the favorite in the first meeting between the teams since the 2024 American League Championship Series. Meanwhile, MLB futures odds have the Yankees behind only the Los Angeles Dodgers at +850 in the odds to win the World Series. Cleveland is at +5000.

Yankees vs Guardians Prediction Today, April  21, 2025

My prediction

• Run Line Pick: New York Yankees -1.5 (+140)

The New York Yankees have won the last three regular-season games when Schmidt pitches against Cleveland and haven’t lost a road series to the Guardians since 2019. The Yankees have won 15 of their last 21 road matchups with the Guardians

Even though the Yankees are just 4-4 on the run line as a road favorite this season, go with New York to win and cover when making MLB expert picks.

Bet on Yankees -1.5 (+140)

• Over/Under Pick: Yankees vs Guardians Under 8.5 Runs (-110)

It was all or nothing for the Yankees in their series with the Tampa Bay Rays, with a pair of shutout victories sandwiched around a game with 18 runs scored. A total of 31 runs were scored in the last three starts for Williams.

Yankees probable starters against the Guardians. #RepBX pic.twitter.com/B2uRmAkFAP

— 161st & River: A Yankees Podcast (@161st_River) April 21, 2025

Each of the last four times that either Schmidt or Williams started in a regular-season MLB matchup between the Yankees and the Guardians, the game landed under the total. That is enough to go with the game going under 8.5 runs when making  MLB game picks.

Bet on Yankees vs Guardians Under 8.5 (-115)

Yankees vs Guardians Prop Picks and Best Bets

• Paul Goldschmidt 2+ Total Bases (+134)

Paul Goldschmidt has made quite the first impression for the Yankees. Some of his best work has come on the road with a .455 batting average. He has at least two hits in seven of his first 10 road games of the season.

Take a look at the +134 MLB player prop picks for the Yankees’ first baseman to have at least two total bases from hits.

Bet on Paul Goldschmidt to have 2+ Total Bases (+134)

• Jose Ramirez 2+ Runs + RBIs (+185)

Jose Ramirez has been putting up impressive numbers on the road. However, he heads into the series opener with three hits (all singles) in 23 at-bats at Progressive Field this season.

Cleveland #Guardians (3B) Jose Ramirez reached base 3x tonight (2-4 2R 2B BB) vs the Pirates including his 4th double of the season that came off the bat at 108.9 mph.

The double moved Ramirez into 5th all-time in franchise history with 368 career doubles.#GuardsBall pic.twitter.com/zIVRFrqpCt

— Guardians Prospective (@CleGuardPro) April 19, 2025

Ramirez is hitting .455 with a slugging percentage of .636 against Schmidt. He could be a solid option to make MLB news today at +185 to have 2+ runs + RBIs.

Bet on Jose Ramirez to have 2+ Runs + RBIs (+185)

• YRFI (-106)

Gavin Williams has allowed four hits and two runs in the first inning of his first four starts of this season. Now he faces a New York lineup with an MLB-leading 38 home runs. The Yankees lead all American League teams with 19 first-inning runs. Enough said.

Bet on Score on First Inning – YES (-106)

Yankees vs Guardians How to Watch

• Game: Yankees (14-8) vs Guardians (12-9)
• Date/Time: Monday, April 21, 6:10 p.m. ET
• Location: Progressive Field, Cleveland, OH
• Yankees vs Guardians Live Stream: MLB.tv

Click here for Yankees vs Guardians betting trends.

Odds and information are accurate at the time of writing. Please check with official sources for the latest updates before placing any bets

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