Strasburg drove a 0-2 pitch into the Orioles bullpen. The home run followed a solo shot by teammate Jesus Flores.
It was Strasburg's 42nd official at-bat in the majors during a career that began in 2010 and was interrupted by elbow ligament surgery.
The homer gave Washington a 5-3 lead. Strasburg singled in his first at-bat against Chen and scored two runs in four innings.