Guardians vs. Tigers Prediction, Odds, Probable Pitchers, Prop Bets for Thursday, May 21

Thursday’s MLB action kicks off with an AL Central battle between the Cleveland Guardians and the Detroit Tigers, two teams going in opposite directions in the standings.

Cleveland has won five games in a row to open up a three-game lead in the division, while the Tigers are in trouble, sitting at 20-30 this season after dropping their last five games. Detroit is just 2-8 in its last 10 games, and the injury to Tarik Skubal has really put the Tigers in a tough spot when it comes to their rotation.

On Thursday, All-Star Casey Mize (2.43 ERA) will take the mound for Detroit in an attempt to stop the bleeding. He’ll go up against lefty Joey Cantillo (3.40 ERA), who has led the Guardians to an 8-2 record in 10 outings this season.

Let’s dive into the odds, a player prop to bet and my prediction for this series finale.

Guardians vs. Tigers Odds, Run Line and Total

Odds via DraftKings Sportsbook

Run Line

Guardians -1.5 (+165)
Tigers +1.5 (-210)

Moneyline

Guardians: -101
Tigers: -120

Total

7 (Over -120/Under -101)

Guardians vs. Tigers Probable Pitchers

Cleveland: Joey Cantillo (3-1, 3.40 ERA)
Detroit: Casey Mize (2-2, 2.43 ERA)

Guardians vs. Tigers How to Watch

Date: Thursday, May 21
Time: 1:10 p.m. EST
Venue: Comerica Park
How to Watch (TV): Tigers.TV/CLEGuardians.TV
Guardians record: 29-22
Tigers record: 20-30

Guardians vs. Tigers Best MLB Prop Bets

Tigers Best MLB Prop Bet

Riley Greene to Hit a Home Run (+740)

Earlier today, I shared in SI Betting’s best home run picks – Daily Dinger – why Greene is worth a long shot bet:

Two-time All-Star Riley Greene has homered just four times in the 2026 season, but he’s been one of the best hitters in baseball. Greene is hitting .333 in the 2026 season, including an impressive .370 batting average against left-handed pitching.

So, I’m buying him against Cleveland Guardians lefty Joey Cantillo, who has given up six home runs in 10 starts, posting a 3.40 ERA and a 4.36 Fielding Independent Pitching.

Greene is 1-for-2 against Cantillo in his career, and the Tigers star is hitting an insane .452 over the last two weeks. The power hasn’t really been there, but at +740, Greene is worth a look since he seems to be a threat to get at least a hit every night.

Guardians vs. Tigers Prediction and Pick

Can Cleveland complete the sweep on Thursday afternoon?

I think the Guardians are a great bet as underdogs in this matchup, especially with Cantillo on the mound. Not only are the Guardians 8-2 in his starts, but the lefty has allowed three or fewer earned runs in eight of his outings.

Cantillo has an expected ERA in the 51st percentile this season, which is worse than Mize (83rd percentile), but he has a much better offense behind him.

The Tigers rank 23rd in MLB in OPS and 26th in runs scored while Cleveland has jumped into the top 10 in the league in run scored and is 15th in OPS.

The Guardians are rolling right now, and it’s hard to pass them by as underdogs, even though Mize has been one of the Tigers’ best arms in 2026. Despite a 2.43 ERA, Mize has led the Tigers to just a 2-5 record in seven starts.

Pick: Guardians Moneyline (-101 at DraftKings)

Odds refresh periodically and are subject to change.

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