The forward - plagued with long-term ankle injuries in recent months - will have had Dortmund hearts racing when he was forced off after suffering a knock in a challenge with Dennis Erdmann midway through the first half.
However, after an opening 45 minutes in which Reus' withdrawal was the only real talking point, Michael Hefele's gaffe handed Ciro Immobile a golden opportunity to get the first of two goals and send Dortmund on their way to the quarter-finals.
The former Torino man made no mistake when afforded possession clean through on goal shortly after the interval and, despite late attacks from the hosts, Dortmund sealed a fourth consecutive quarter-final appearance with Immobile's second.
Immobile tapped home from Jakub Blaszczykowski's cross to double the advantage, with Reus ending the game back on the Dortmund bench - easing fears over his injury ahead of next week's UEFA Champions League last 16 second leg clash with Juventus.
After an even opening 10 minutes, in which neither side were able to test the opposing goalkeeper, Dortmund were dealt an early below when Reus hobbled off in some discomfort after injuring his left knee in a tackle.
Henrikh Mkhitaryan was the man chosen to replace the Germany international before Dresden saw shouts for a penalty waved away when Niklas Kreuzer went down inside the area under pressure from Neven Subotic.
Justin Eilers - hat-trick hero in Dresden's 3-2 win over Jahn Regensburg at the weekend - was denied the opportunity to test Roman Weidenfeller before the break by an offside flag, despite the forward appearing to be in his own half when the ball was played.
Having survived that scare prior to the interval, Dortmund led five minutes into the second period when captain Hefele undid his side's positive opening 45 minutes with a moment of madness.
The defender sought to switch the play to the opposite flank, but instead found Immobile in acres of space, with the Italian slotting home his first goal since mid-December.
When Mats Hummels slipped, Mitchell Langerak was forced to stand tall and deny Eilers as the hosts refused to give up on causing an upset.
Dortmund's progression should have been sealed when Mkhitaryan fired Oliver Kirch's delivery high over the crossbar before the hour, but Immobile's second in the 90th minute ended any Dresden hopes.
Ilkay Gundogan found Blaszczykowski down the right, with the Poland midfielder squaring for the striker to tap home.
Immobile's second wrapped up a relatively comfortable outing for Jurgen Klopp's men, who continue their revival and extend their winning run to five matches in domestic competition.
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