The Armenian star struck in each half to cancel out Vaclav Kadlec's goal and sees BVB leapfrog Bayern Munich with four wins from four in the Bundesliga.
The Armenian struck either side of Vaclav Kadlec's goal to see Jurgen Klopp's side leapfrog Bayern Munich with its fourth win in four league games against a spirited Frankfurt side.
Dortmund made one change from a 1-0 win over Werder Bremen last week, with Sven Bender replacing Sebastian Kehl in midfield.
For the home side, recent signings Stephan Schrock and Kadlec both featured in the starting lineup as Armin Veh's men went in search of consecutive Bundesliga wins.
Frankfurt started brightly and created an early chance when Japan international Takashi Inui tested Dortmund goalkeeper Roman Weidenfeller.
At the other end, Marco Reus set up Jakub Blaszczykowski, but he could only fire straight at keeper Kevin Trapp.
Dortmund did score an early goal though, as Armenian Mkhitaryan calmly slid home a through ball.
Blaszczykowski slipped the ball in behind the Frankfurt defense and Mkhitaryan did the rest, timing his run well before slotting a left-footed effort past Trapp.
Kadlec had a terrific chance to level proceedings but was denied by good defending from Marcel Schmelzer, before Weidenfeller kept out the dangerous Czech forward moments later.
Kadlec was a constant threat though, and opened his Frankfurt account 10 minutes before the break after reacting quickly to a loose ball, knocking home the rebound from Stefan Aigner's cross to send the sides level into the break.
Parity was not to last long, however, as Mkhitaryan fired home his second of the afternoon within 15 minutes of the restart. The attacking midfielder cut in from the right before dribbling along the edge of the penalty area and striking powerfully past Trapp.
Dortmund almost scored a third goal shortly after, but defender Neven Subotic saw his header hit the post.
The visiting side enjoyed good spells of possession in the latter stages but could not find another goal to kill the game off.
Dortmund held on for victory though, as Jurgen Klopp's men – who have lost just two Bundesliga matches on the road since Sept. 2011 - made it four wins from as many games this season, leapfrogging champion Bayern Munich into first place in the table.