Werner was staked to a three-run lead in the first inning and held on for the milestone victory that extended the Padres' winning streak to four.
He had made only four starts at the Class AAA level, with a 5.79 ERA, before being called up.
All of the San Diego runs came off James McDonald (11-6), who allowed five hits with five walks in five innings.
The Pirates have lost three straight.
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