Dortmund took a deserved early lead through Pierre-Emerick Aubameyang's tap-in before Marco Reus slotted home on the stroke of half-time as the visitors looked on course for a second successive league win.
But Lukas Rupp gave the hosts hope midway through the second half with a terrific individual strike before Reus' afternoon ended following a strong challenge from Marvin Bakalorz, who was arguably lucky to only be given a yellow card.
That injury noticeably rocked Jurgen Klopp's men, who had a Kevin Grosskreutz effort ruled out for offside when Dortmund led 2-1.
And Paderborn took full advantage of the reprieve to earn a share of spoils, levelling eight minutes from time through Mahir Saglik's header.
It was certainly an eventful afternoon for the visitors and Reus, with head coach Klopp admitting earlier in the week that the German international could be tempted by a move away from Dortmund.
The 25-year-old nearly gave Dortmund the best possible start within just two minutes, with goalkeeper Lukas Kruse having to be alert to smother after a cutting throughball from Henrikh Mkhitaryan.
That early chance set the tone for the game as the visitors enjoyed the best of the opening exchanges.
And they were rewarded after 12 minutes when Erik Durm found some space on the left and picked out Aubameyang with an inch-perfect cross that he finished with a simple tap-in from close range.
Paderborn kept battling, though, and nearly drew themselves level seven minutes later when Suleyman Koc burst into the box to force a good save from Roman Weidenfeller after latching on to Bakalorz's incisive pass.
But Dortmund continued to look the better side, with Aubameyang twice firing wide after 25 minutes before Mkhitaryan saw an effort ruled out for offside.
Koc curled a free-kick wide for the hosts five minutes before the break, but Dortmund ended the half two goals to the good courtesy of Reus, who was on hand to finish a fine move that saw the defence split open by Aubameyang's deft first-touch pass.
Reus nearly doubled his tally just after the restart, but his angled drive was well saved by Kruse, who was also at full stretch to deny Aubameyang 10 minutes later.
Dortmund's failure to notch a third was punished on the hour, when Rupp shook off the attentions of Neven Subotic and Grosskreutz to burst into the area and slot home.
Things got worse for the visitors seven minutes later when a cynical challenge from Bakalorz forced Reus off with a suspected ankle injury.
Grosskreutz should have sealed the win 17 minutes from time, but the substitute could only fire wide after breaking free of the home defence and he then had another effort controversially ruled out for offside 10 minutes from time.
And Paderborn made Dortmund pay courtesy of Saglik's header, ensuring an eventful end to the first competitive meeting between the two sides.