Watch: Dortmund go nine points clear
With defending champions Bayern hosting Stuttgart on Sunday, Dortmund grabbed the chance to thump second-from-bottom Hanover with Reus causing havoc on his return from an ankle injury.
"We took our time to find the gaps, but after we changed ends and went 2-0 up it was much easier," said Dortmund coach Lucien Favre after his side floored Hanover with three goals in seven minutes.
Achraf Hakimi, on loan from Real Madrid, Reus, Mario Goetze and Raphael Guerreiro scored Dortmund's goals to keep them on course for their first Bundesliga title since 2012.
The rout piles pressure on Hanover coach Andre Breitenreiter, but his side showed spirit when Marvin Bakalorz scored a late consolation against his former club before Witsel grabbed Dortmund's fifth goal on 90 minutes.
"It's up to others in the club to decide now where we go from here," said Breitenreiter, who helped Hanover win promotion back to the Bundesliga last season.
"This isn't about me - it's about staying up."
Hanover started brightly at Dortmund's Signal...