Velasquez, who turned 23 Sunday, and was 3-0 with a 1.37 ERA in five starts at Double-A Corpus Christi. Velasquez will become the second top Astros prospect to debut in three days, following shortstop Carlos Correa on Monday.
Utilityman Jonathan Villar was optioned to Triple-A Fresno following Tuesday's game. Villar was hitting .263 in 38 games.
Houston leads the AL West but has lost six consecutive games.