Cleveland Guardians vs Philadelphia Phillies Prediction, Preview and Odds - 05/22/2026

Game Time: 6:40 pm ET, Friday, May 22, 2026

Venue:  Citizens Bank Park, Philadelphia, PA

Where to Watch:  MLB TV

DraftKings:  Moneyline odds:  Guardians +149, Phillies -182; Over/Under:  7 runs

Bet365:  Moneyline odds:  Guardians +150, Phillies -180; Over/Under:  7 runs

BetMGM:  Moneyline odds:  Guardians +150, Phillies -185; Over/Under:  7 runs

Cleveland Guardians:  29-22 (1st place, AL Central)

Philadelphia Phillies:  25-25 (2nd place, NL East)

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Cleveland Guardians:  8-2 last 10

Philadelphia Phillies:  7-3 last 10

The Guardians are entering this series off a win and completed the sweep in their 4-game series against the Detroit Tigers 4-0 in their last series. They enter this game with a 30-22 record overall and have a road record of 15-12. This is the series opener of a 3-game series with the Phillies on Friday. Their offense ranks 15th in the MLB with a .702 OPS. Joey Cantillo was their starting pitcher on Thursday while Gavin Williams is making his start in this game on Friday. He is 6-3 with a 3.67 ERA this season. His team lost 2 of their last 3 games this season with him making an appearance. In his last MLB regular season appearance, he allowed 2 ER, 1 HR, and 0 BB with 7 SO on 8 hits through 6 IP against the Cincinnati Reds.

The Phillies are entering this series off a loss and lost their 3-game series against the Cincinnati Reds 2-1 in their last series. They enter this game with a 25-25 record overall and have a home record of 13-14. This is the 1st game of a 3-game series with the Guardians on Friday and they have Thursday off as a day of rest. Their offense ranks 22nd in the MLB with a .693 OPS. Aaron Nola was their starting pitcher on Wednesday while Cristopher Sánchez is making his start in this game on Friday. He is 5-2 with a 1.82 ERA this season. His team won their last 4 straight games this season with him making an appearance. In his last MLB regular season start, he allowed 0 earned runs, 0 homers, and 0 walks with 13 strikeouts on 6 hits through 9 innings pitched against the Pittsburgh Pirates.

The current betting odds have the Phillies listed as a favorite in this game according to Draftkings Sportsbook. The Phillies have looked good in their games this season with their 25-25 record overall which has them right near the top of the NL East. They haven't looked great in their own ballpark though with their 13-14 home record this season. Meanwhile, the Guardians have looked good in their games this season with their 29-22 record overall which has them right at the top of the AL Central. They have been a good road team too with their 15-12 road record this year. The Guardians are 8-2 in their last 10 games and they have been rolling lately, sweeping the Tigers in a 4-game series right before this. The Phillies have also been getting hot though, going 7-3 in their last 10 games, and they will be looking to bounce back from a series loss. Their offense has been improving lately and they have looked a lot better since firing their manager. They are going with Sanchez in this one and he has been their ace this season, coming off a great year too. He is 5-2 with a 1.82 ERA and he doesn't give up many runs. He is off another great start in which he gave up no runs, something that has been a common theme for him this season, and the team has won 4 games in a row now with him starting too. Williams is on the mound for the Guardians in this one and he has looked good this year. He is 6-3 with a 3.67 ERA, but lately the team has had some trouble with him. He only gave up 2 earned runs in his last start, but he has been giving up more runs lately and the team has lost 2 of their last 3 games with him starting too. The Guardians are due for a let down after sweeping the Tigers in 4 games and the Phillies should be able to edge them out at home with their best starter on the mound. The best way to place a bet here is on the Phillies to win this game. 

Guardians Phillies Prediction:  Our MLB Pick for Friday, May 22, 2026 (6:40 pm ET start time) is Phillies 3 Guardians 2.

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Cleveland Guardians: 19-13 (+8.3 units) on the moneyline against NL East opponents. 214-173 (+37.7 units) on the moneyline in all games. 100-93 (+21.6 units) on the moneyline in road games. 22-11 OVER vs. NL teams allowing 4.5 or more runs/game on the season.

Philadelphia Phillies: 89-66 (-6.8 units) on the moneyline as a favorite of -125 to -175. 97-96 (-15.8 units) on the moneyline when playing against a team with a winning record. 25-25 (-6.5 units) on the moneyline in all games. 9-5 OVER at home when the total is 7 or less.

Cleveland Guardians:  G. Arias (SS) Ten Day IL - Hamstring.

Philadelphia Phillies:  K. Schwarber (DH) Day To Day - Illness. K. Backhus (RP) Fifteen Day IL - Elbow. M. Lazar (RP) Sixty Day IL - Oblique. Z. Pop (RP) Fifteen Day IL - Calf.

“Tanner, eight innings, did his job, kept us in that game. We're having a tough time scoring runs for Tanner so far this year, but credit to our guys who stayed in it, didn't quit, got the 9th inning rally going. But Tanner was definitely the player of the game.” - Stephen Vogt after his team’s win against the Tigers in their game on Wednesday. 

“Don has been around a lot of baseball, a lot of really good baseball. He’s seen it all. As much as you can see from a player’s perspective, a coach’s perspective, a manager’s perspective. He’s been on all sides of the game.” - Alec Bohm on Don Mattingly as the new manager.

Daniel Schneemann (L) 3B

José Ramírez (S) DH

Chase DeLauter (L) RF

Rhys Hoskins (R) 1B

Travis Bazzana (L) 2B

Angel Martínez (S) LF

Steven Kwan (L) CF

Patrick Bailey (S) C

Brayan Rocchio (S) SS

Trea Turner (R) SS

Adolis García (R) RF

Bryce Harper (L) DH

Alec Bohm (R) 1B

J.T. Realmuto (R) C

Brandon Marsh (L) CF

Edmundo Sosa (R) 3B

Bryson Stott (L) 2B

Otto Kemp (R) LF

Batting Average:  Travis Bazzana (.296)

Hits:  Chase DeLauter (46)

Home Runs:  Angel Martínez (9)

RBI:  Chase DeLauter (30)

Stolen Bases:  José Ramírez (20)

Wins:  Gavin Williams (6)

Saves:  Cade Smith (16)

ERA:  Tim Herrin (1.15)

Batting Average:  Brandon Marsh (.325)

Hits:  Brandon Marsh (54)

Home Runs:  Kyle Schwarber (20)

RBI:  Kyle Schwarber (36)

Stolen Bases:  Bryson Stott (9)

Wins:  Cristopher Sánchez (5)

Saves:  Jhoan Duran (8)

ERA:  Jhoan Duran (1.42)

Managers:

Cleveland Guardians: Stephen Vogt (3rd season)

Philadelphia Phillies: Don Mattingly (Interim)