The home side were slicing through a weakened Tottenham line-up in the opening 20 or so minutes with Aubameyang volleying over the target from close range before knocking in a Hugo Lloris save from Henrikh Mkhitaryan's long range attempt only to be flagged offside.
The opening goal came on the half-hour mark when Marcel Schmelzer found space out on the left to pick out the prolific Aubameyang in the area and the African Player of the Year made no mistake with his header, placing it just inside Lloris' let upright to notch his eighth goal in Europe this season and 33rd in all competitions.
Dortmund's scything attack diminished somewhat following the first goal but they almost doubled their advantage on 50 minutes only to see Gonzalo Castro's angled effort hit the woodwork.
Just after the hour-mark, however, BVB were two to the good and the Yellow Wall was again rocking when Neven Subotic glanced a header after a short corner to the back post where Reus was on hand to emphatically fire home a volley from pointblank range.
In the 70th minute, Dortmund had drawn the curtains on Tottenham with a devastating move which resulted in Aubameyang finding Castro who clipped a lovely ball into the path of Reus who produced a quality side-footed half-volley for his second of the game and 10th of the European campaign.
The three-goal difference makes life extremely difficult for Spurs in the return bout at White Hart Lane next Thursday but on the bright side, an early exit form this competition will give the North Londoners more focus on chasing their first top flight English title since 1961.
2015/16 UEFA Europa League - Round of 16 first leg