Houston Astros vs Cleveland Guardians Prediction, Odds and Picks for Today, 04/21/26

The Houston Astros picked up a 9-2 road win in the series opener against the Cleveland Guardians, collecting 13 hits, while snapping a four-game skid, including a weekend sweep at home in an interleague series against the St. Louis Cardinals. The win in the series opener also snapped a five-game losing streak against American League opponents, and the road victory was just the second of the season in 11 tries. Houston entered Monday’s game just 1-9 in 10 road games. The nine runs were the most for the Astros since going for 11 and 10 runs in back-to-back games in Sacramento against the A’s on April 4-5.

The Guardians took three of four games from the Baltimore Orioles over the weekend, and the first-place Guardians were feeling good about themselves. The nine runs allowed were the most since getting dusted 13-1 on Sunday Night Baseball in Atlanta on April 12. The Over has cashed in three of the past four games, with Cleveland pitching allowing 5.3 runs per game (RPG) in the past four outings. Houston has cashed high in four consecutive games, and six of the past eight outings. Let’s go high in this matchup between RHP Ryan Weiss and LHP Parker Messick. The Under cashed in Weiss’ first start on Thursday, while the total has gone low in three of Messick’s four outings to date.

Under 8 (-105) at time of publishing. Playable to -120.