Goals from Dusan Tadic, Sebastien Haller and Davy Klaassen in the last 19 minutes maintained the Dutch club's 100% record after Marco Reus had converted a first-half penalty for the home team, who had to play for an hour with 10 men after Mats Hummels was sent off.
Ajax moved to 12 points at the top of the standings and booked a place in the last-16 with two matches to play. Dortmund share second spot with Sporting CP on six points.
Brazilian winger Antony proved the inspiration for Ajax by providing the crosses for all their goals and he was involved in the controversial dismissal of Hummels.
They were left-footed crosses from the right wing, first for Tadic to steer the ball home at the back post in the 71st minute, then for Haller to continue his scoring form in the competition with a flicked header seven minutes from time before Klaassen completed the scoring.
It had taken the visitors time to break down their hosts and take advantage of their numerical superiority.
English referee Michael Oliver had no hesitation in red carding the experienced Germany defender Hummels in the 28th minute for a sliding tackle on the halfway line on Antony.
Television replays, however, showed that Antony had narrowly avoided contact but after a Video Assistant Referee review, Oliver's decision was upheld to the astonishment of the home side.
Seven minutes later the referee was encouraged to check his initial decision to turn down Jude Bellingham's appeals for a penalty after tumbling down in the Ajax penalty area as he was sandwiched in by two defenders.
Oliver reviewed the action on the screen at the side of the pitch and found that Ajax full back Noussair Mazraoui had impeded Bellingham's attempt to shoot, then awarding the spot-kick that Reus converted in the 37th minute.
The Germans had been soundly beaten 4-0 by Ajax a fortnight earlier and were playing without top scorer Erling Haaland but showed tenacity and a fighting spirit before crumbling at the end.