Harrell (7-6) allowed only two hits in seven innings during his previous start, but still suffered a 2-0 loss against Cleveland.
He struck out seven Padres Wednesday and boosted the Astros to their fourth win in five games.
The only run came in the third, when Matt Downs led off the inning with a home run off Clayton Richard (5-8). The setback ended Richard's three-start winning streak.
Harrell is in his third season in the majors, having started with the Chicago White Sox before coming to the Astros during the 2011 campaign. This was the 21st start of his career.