Erling Haaland's absence through injury and Leipzig boss Julian Nagelsmann's upcoming move to Bayern dominated the pre-match chat, but Dortmund took it all in its stride.
After surviving an early scare when Marwin Hitz thwarted Leipzig's Hwang Hee-chan one-on-one, Dortmund forged ahead through captain Marco Reus.
The Germany international started the move with a brilliant dummy of Lukasz Piszczek's inside pass, before continuing his run, collecting Thorgan Hazard's cool flick and firing beyond Peter Gulacsi with aplomb.
The hosts' electric start gave way to a more measured approach for the remainder of the half, albeit with Dortmund asking all the questions.
Hazard tested Gulacsi with a shot from inside the area, while Sancho drove into the side netting from a similar position after a lightning counter-attacking move.
Leipzig showed signs of life soon after the restart as Marcel Sabitzer warmed the palms of substitute goalkeeper Roman Bürki – on at half-time for the injured Hitz – but was given a mountain to climb in the 51st minute after Sancho scored his first.
Raphael Guerreiro fed the England star, who cut inside of his marker and curled a precision-perfect strike into the far corner of Gulacsi's goal for 2-0.
Dortmund appeared to be in complete control, but was pegged back just past the hour when Lukas Klostermann headed home Emil Forsberg's corner. Leipzig tails up, substitute Justin Kluivert found the side netting before Dani Olmo turned in a cross from Hwang to level the scores.
Dayot Upamecano denied Reus a clear sight of goal in the closing stages, but there was no stopping Sancho, who capped a superb team move with a late winner that ensured the Bundesliga title would stay un Munich for another season, even before Bayern had kicked off its 6-0 demolition of Borussia Moenchengladbach.
With two games to go, the Black-Yellows could yet join the record champion in the 2021-2022 UEFA Champions League having moved two points above a fading Eintracht Frankfurt into fourth spot on the table, with Frankfurt looking to regain its position against Mainz later on Sunday (AEST).