The Bundesliga giants thumped the Premier League title-chasers at Signal Iduna Park, with Mauricio Pochettino naming an under-strength side against Thomas Tuchel's men
Both sides sit second and five points off the top in their respective leagues, but Spurs boss Mauricio Pochettino controversially opted to make seven changes to his team and paid the price in Germany.
Aubameyang headed in his 33rd goal in 38 appearances this season in the first half, before a clinical double from Reus after the break put Thomas Tuchel's men in a dominant position.
Gonzalo Castro hit the post prior to Reus' strikes in a match that could have been even worse for Spurs, who lacked any serious attacking threat without Harry Kane in the starting line-up and now know their continental hopes are all but over this season.
Spurs' only attempt on target in the first half came in the opening minute, with Christian Eriksen's long-range strike testing Roman Weidenfeller, one of two players to come into the hosts' team.
The other, Castro, fired over from Reus' knockdown in response, before Erik Durm shot wide on the stretch in a decent opening created by Aubameyang.
Aubameyang was causing problems and he volleyed just over after an exchange of passes with Marcel Schmelzer and then had a goal ruled out.
Spurs goalkeeper Hugo Lloris made a superb save to keep out a left-footed thunderbolt from Henrikh Mkhitaryan and Aubameyang converted the rebound, only to be rightly flagged for offside.
The Gabon international was not to be denied on 30 minutes, though. Dortmund worked an opening on the left when Castro fed Schmelzer and the full-back's sweeping cross was firmly headed into the bottom corner by Aubameyang from eight yards out.
Dortmund came close to a second early in the second half when Aubameyang latched on to Mkhitaryan's pass. The striker's attempted chip over Lloris was drifting wide until Castro intervened, but he could only hit the foot of the post from a tight angle.
Son Heung-min then went down under pressure from Sven Bender in the box at the other end in a rare foray forward for Spurs, but referee Cuneyt Cakir was unmoved and the home side then doubled their lead after 61 minutes.
A cleverly worked corner led to Castro's cross being headed on by substitute Neven Subotic and Reus finished emphatically, smashing a shot into the roof of the net from a yard out at the far post.
And nine minutes later it was three. Aubameyang found Castro, who in turn chipped through a pass for Reus in the penalty area to confidently side-foot past Lloris.
Son's effort was kept out by Weidenfeller and Kane was finally brought off the substitutes' bench with 14 minutes remaining, but there was to be no vital away goal on a miserable outing for Pochettino's men.