The Houston Astros broke out the lumber on Monday night, scoring a 9-2 series-opening victory over the Cleveland Guardians.
With the momentum clearly in Houston’s favor, my Astros vs. Guardians predictions expect another 'Stros victory tonight.
Read on for my MLB picks for Tuesday, April 21.
Who will win Astros vs Guardians today: Astros moneyline (+125)
Ryan Weiss doesn't need to be perfect today. He just needs to give the Houston Astros enough solid innings before their offense takes over.
The Astros have the second-best offense in baseball with a 124 wRC+, while the Cleveland Guardians check in at exactly league average with a 100 wRC+.
That gap matters late in a game when both starters are likely on short leashes; Parker Messick takes the hill after 112 pitches Thursday, while Weiss hasn’t gone more than 3 2/3 frames.
Back the better bats in this one.
COVERS INTEL: Yordan Alvarez owns a .541 xwOBA and 1.261 OPS, and is tied for first in the American League with 21 RBI. 
Astros vs Guardians Over/Under pick: Over 8.5 (+100)
Two possibly compromised starters, and two bullpens prone to the long ball.
This game has runs written all over it.
Messick boasts an xFIP that’s two runs higher than his ERA and is likely on a shorter leash. Weiss owns a 13.9% walk rate and has struggled to keep hitters off the bases all season.
Neither bullpen is anything to trust. Cleveland’s bullpen allows 1.54 home runs per nine innings, while Houston’s relief corps gives up 1.89.
With four of their previous six games going Over the total, we’ll back the bats in this one.
- ML/RL bets: 3-4, -0.35 units
- Over/Under bets: 3-3, -0.06 units
Astros vs Guardians odds
- Moneyline: Astros +127 | Guardians -133
- Run line: Astros +1.5 (-150) | Guardians -1.5 (+144)
- Over/Under: Over 8.5 (+108) | Under 8.5 (-122)
Astros vs Guardians trend
The Astros have hit the Over in 11 of their last 16 games (+5.20 Units / 29% ROI). Find more MLB betting trends for Astros vs. Guardians.
How to watch Astros vs Guardians and game info
| Location | Progressive Field, Cleveland, OH |
| Date | Tuesday, April 21, 2026 |
| First pitch | 6:10 p.m. ET |
| TV | SCHN, CleGuardians.TV |
| Astros starting pitcher | Ryan Weiss (0-2, 6.75 ERA) |
| Guardians starting pitcher | Parker Messick (3-0, 1.05 ERA) |
Astros vs Guardians latest injuries
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Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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