A fit again Erling Braut Haaland slotted straight back into Dortmund's attack from injury, but goalkeeper Marwin Hitz had his spot taken by Roman Burki following a knee injury.
Leipzig were hit with an early blow after five minutes with an opening from Mahmoud Dahoud playing in Jadon Sancho to go on and curl into the top right-hand corner.
The Black and Yellow made it two a few minutes from the half-hour mark after Haaland overpowered Dayot Upamecano to slide home a cutback from Marco Reus.
A third seemed probable in the 31st minute after a pass from Sancho connected with Dahoud, who went and fired wide of goalkeeper Paul Gulacsi's goal from outside the area.
Sancho took matters in his own hands on the stroke of halftime after he danced around the defence from a square ball by Reus to find the net from inside the box.
Leipzig put on a double change at the interval in Christopher Nkunku and Yussuf Poulsen, whereas Dortmund threw in Thorgan Hazard for Jude Bellingham.
Julian Nagelsmann, who will managed Bayern Munich next season, watched the substitutes combine to go on and rattle the crossbar from a volley by Nkunku.
The two was at it again a little before the last 30 minutes when a low cross from the right by Poulsen spotted Nkuku, who put Burki to work with a smart effort.
Nagelsmann's side did found a goal on 71 minutes following a first-time strike from Dani Olmo, which arrowed into the left-hand corner.
Dortmund remained under threat within seconds through Konrad Laimer and a snap shot from Emil Forsberg that struck the post.
However, Haaland erased Leipzig's hopes of a turnaround in the last three minutes when he got on the end of a counter-attack by Sancho to find the net and see his side crowned DFB-Pokal winners.