Astros vs. Guardians odds, line, prediction: 2026 MLB picks for Tuesday, April 21 from proven model

A pair of American League teams will meet for the second of a three-game set on Tuesday's MLB schedule as the Houston Astros visit the Cleveland Guardians. Houston (9-15) ended a four-game losing streak by taking Monday's contest 9-2. Cleveland (13-11) was 5-1 in series openers before losing yesterday. Ryan Weiss (0-2, 6.75 ERA) will take the mound for the Astros, while the Guardians will counter with Parker Messick (3-0, 1.05 ERA).

First pitch is at 6:10 p.m. ET from Progressive Field in Cleveland. The latest Guardians vs. Astros odds list Cleveland as the -132 favorite on the money line (risk $132 to win $100). The over/under for total runs is 8.

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The model has simulated Guardians vs. Astros 10,000 times and the results are in. The model is going Over on the total, and is also says one side of the money line has ALL the value!

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