The two sides played out a 1-1 draw in the first leg of the last-16 tie in Germany last week, but it was Dortmund who conquered the return fixture in France - despite falling behind through an awful goalkeeping error.
Lille hit the visitors on the counter attack in the fifth minute with left-back Ismaily squaring for Jonathan David, with goalkeeper Gregor Kobel inexplicably allowing his tame shot to pass between his legs.
Dortmund pressed forward in search of an equaliser and came close to breaking through on several occasions, but their first-half attempts were rebuffed by the fantastic reactions of goalkeeper Lucas Chevalier.
The German side were gifted the equaliser early in the second period when their former player Thomas Meunier was ruled to have brought down Serhou Guirassy in the box and Emre Can stepped up to level matters.
A Dortmund winner seemed imminent as Niko Kovac's team stepped up their game. Shortly after Karim Adeyemi had hit the crossbar and Pascal Gross missed with a header, Maximilian Beier managed to turn inside the box and lash home what proved to be the winner in the 65th minute.