Marco Reus has handed Borussia Dortmund a 1-0 half-time lead over Mainz 05 at the Coface Arena.
The first opportunity of the evening fell to Mainz when the visitors were caught in possession high up the pitch, which allowed Pierre Bengtsson to cross for Yoshinori Muto, whose close-range effort was kept out by Roman Burki.
Dortmund's eagerness to press the hosts in possession saw them become more dangerous as the first half progressed, and they were ahead in the 18th minute thanks to a mistake from Niko Bungert.
A poor pass from the Mainz defender fell to the feet of Mkhitaryan, who combined with Pierre-Emerick Aubameyang to pick out Reus, and the Germany international made no mistake with a calm low finish after finding himself in space inside the box.
Mainz could have hit back immediately when Park Joo-ho's error allowed the hosts to attack in numbers, but Yunus Malli could only drag his effort wide after being released by Pablo de Blasis.
The home side continued to threaten and came close to equalising once again when Jairo Samperio's free kick was tipped over by Burki.