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Paderborn, who are bottom of the Bundesliga, raced into a shock three-goal lead in the first-half at Signal Iduna Park thanks to a Streli Mamba brace and Gerrit Holtmann strike.
Dortmund also lost star striker Paco Alcacer, who was substituted with an injury as his teammates were booed off at half-time.
The enforced change did not stop Dortmund boss Lucien Favre bringing on Achraf Hakimi and Thorgan Hazard for the second-half, which used up all of his available substitutes.
Hakimi made an immediate impact, assisting Sancho’s first goal in nine games as he slotted past Paderborn goalkeeper Leopold Zingerle in the 47th minute.
The match looked to be petering out before Alex Witsel pulled another goal back with six minutes remaining.
And Dortmund captain Marco Reus completed the stunning comeback when he headed home an inch perfect cross from Sancho in the second minute of stoppage time.
Sancho’s goal and assist could kickstart his campaign after so far struggling to replicate his 2018/19 form.
The England winger scored 12 goals and registered 14 assists in the Bundesliga last season, but has appeared unsettled in Germany in recent months.
The 19-year-old was dropped from the matchday squad against Borussia Monchengladbach for arriving back late from international duty last month and was substituted after just 36 minutes in a 4-0 defeat to Bayern Munich.
Despite the jubilation of coming back from 3-0 down, Dortmund missed the chance to move to within three points of Bundesliga leaders Borussia Monchengladbach, who face Union Berlin on Saturday.
Favre’s side could finish the weekend as low as ninth if results go against them.
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