Astros vs. Guardians Prediction, Odds, Probable Pitchers, Prop Bets for Wednesday, April 22

An afternoon rubber match is set for Wednesday, April 22 between the Houston Astros and Cleveland Guardians, after Cleveland picked up a 8-5 win on Tuesday to even the series.

These teams have combined for 11 and 13 runs in the first two games of this series, yet oddsmakers have set the total for Wednesday’s game at just 8 runs. The Guardians are favored at home, as Houston (9-16) is off to a 2-10 start on the road.

Peter Lambert (7.20 ERA) is set to make his second appearance of the season for the Astros after allowing four runs and seven hits in his 2026 debut against the St. Louis Cardinals. He’ll match up against Cleveland’s Tanner Bibee (4.81 ERA), who is coming off his best start of the season, tossing six innings of scoreless ball against the Baltimore Orioles.

Despite that, Cleveland is just 1-4 in Bibee’s five starts, making it tough to trust the Guardians as -143 favorites on Wednesday.

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

Astros vs. Guardians Odds, Run Line and Total

Odds via DraftKings Sportsbook

Run Line

Astros +1.5 (-186)
Guardians -1.5 (+153)

Moneyline

Astros: +119
Guardians: -143

Total

8 (Over -110/Under -110)

Astros vs. Guardians Probable Pitchers

Houston: Peter Lambert (0-1, 7.20 ERA)
Cleveland: Tanner Bibee (0-2, 4.81 ERA)

Astros vs. Guardians How to Watch

Date: Wednesday, April 22
Time: 1:10 p.m. EST
Venue: Progressive Field
How to Watch (TV): Space City Network, CLEGuardians.TV
Astros record: 9-16
Guardians record: 14-11

Astros vs. Guardians Best MLB Prop Bets

Astros Best MLB Prop Bet

Yordan Alvarez to Hit a Home Run (+371)

In today’s best home run picks for SI Betting, I broke down why Alvarez is primed to stay hot against Cleveland:

Alvarez has been one of the hottest players in MLB this season, hitting .330 with 10 homers and an insane 1.203 OPS.

He’s been even better over the last week, hitting .355 with four home runs over his last seven games. So, it’s shocking that he’s still north of +300 to hit a homer in this series finale with the Cleveland Guardians.

Cleveland has righty Tanner Bibee on the mound in this matchup, and he’s given up four home runs in five starts, posting a 4.81 ERA. Last season, the right-hander allowed 27 home runs in 31 starts, so he’s certainly prone to giving up a long ball or two.

Alvarez has limited at-bats against Bibee in his career, but he comes into Wednesday’s matchup with a 1-for-3 line, doubling for his lone hit against him.

I think the Houston slugger has been too good to pass up at this price, especially since Cleveland’s bullpen (5.04 ERA in 2026) has given up 14 homers as well this season.

Astros vs. Guardians Prediction and Pick

One blowup outing – eight runs against the Atlanta Braves – has really altered Bibee’s ERA this season, but I’m still taking the OVER in this matchup.

Houston has the best OVER record in MLB (18-7) so far this season, and it profiles as the ideal OVER team.

The Astros rank second in OPS and third in runs scored on offense while posting the worst team ERA (6.05) in MLB. On top of that, Houston has a bullpen ERA of 5.91, so even once Lambert exits this game, there’s a chance the Astros still give up a bunch of runs.

Cleveland’s bullpen (5.04 ERA) hasn’t been much better, which is why the team has won just one of Bibee’s five starts. After the righty spun six scoreless innings against Baltimore, the Guardians still found a way to lose that game 6-4.

I simply don’t trust either pitching staff in this matchup, so I’ll gladly take the OVER on a rather low total in this series finale.

Pick: OVER 8 (-110 at DraftKings)

Odds refresh periodically and are subject to change.

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