Fresh from more of his habitual heroics against Paris Saint-Germain in midweek, the in-form Nkunku went close to breaking the deadlock when he plotted a path through the Dortmund defence but was denied by Gregor Kobel. Following up, Dominik Szoboszlai turned the rebound wide of the far post.
Nkunku was proving to be a menace every time he touched the ball and when Josko Gvardiol threaded a perfectly weighted pass into his path, there could only be one outcome.
The Frenchman skipped past Kobel and tucked the ball into the open goal, giving Leipzig a deserved lead.
Dortmund managed to muster only one shot on goal in the first 45 minutes, and that was blocked by its own player with Donyell Malen getting in the way of Jude Bellingham's effort.
Dortmund reorganised at the start of the second half with Thorgan Hazard taking his place in a four-man defence, and the change in tactics opened gaps in the Leipzig armoury.
Thomas Meunier took a leaf out of the Gvardiol book of assists with a perfectly timed and executed pass for Marco Reus, whose first touch was outstanding to set himself up for a sweeping shot past Peter Gulacsi to bring the guests level.
Kobel then made a remarkable double save, first to deny Mohamed Simakan and then, while falling to the ground, kicking the ball away from Szoboszlai with his trailing leg.
The irresistible Nkunku almost restored Leipzig's lead when he waltzed his way through the Dortmund defence and sent a low shot against the post, before he set up Poulsen to restore Leipzig's advantage from close range.
Nordi Mukiele had a goal ruled out for offside as the hosts looked to turn the screw, but another goal was not needed as Leipzig took the spoils in style, and Dortmund lost ground on Bayern Munich after the champion opened up a four-point lead with its victory over previously unbeaten SC Freiburg.