Werder had the chance to go level on points with Bayern Munich at the top in the event of a victory and they dominated the first-half at the Weserstadion, only to fall behind three minutes before half-time to Ivan Perisic's stunning strike.
The Croatian had already showcased his rifle-like left foot in last month's Champions League draw with Arsenal, and another vicious hit on Friday handed the hosts' stand-in 'keeper Sebastian Mielitz no chance.
However, Perisic left his teammates up against it when he was sent-off within moments of the restart, seeing a second yellow card for a late tackle on Sokratis Papastathpoulos.
Lukas Schmitz almost levelled with a deflected shot that came back off the Dortmund crossbar, but soon after Jürgen Klopp's men doubled their lead.
Bremen failed to fully clear a corner, and when Mats Hummels headed the ball back into the six-yard box, Patrick Owomoyela was on hand to stab past Mielitz.
It was the perfect way for Owomoyela to mark his first appearance after six months out injured.
The win - their third on the bounce in the league - is the perfect boost for Dortmund ahead of their Champions League trip to Olympiakos on Wednesday.
On Saturday, leaders Bayern Munich - who have not conceded a goal since the opening day of the season - play host to Hertha Berlin.
Borussia Mönchengladbach can go clear in second with a win at home to Bayer Leverkusen, while Schalke take on Kaiserslautern.
Bottom of the table Hamburg appointed former Bayern Munich player Thorsten Fink as their new coach this week, but he will only take charge on Monday, meaning sporting director Frank Arnesen will be in the dugout for Sunday's game at Freiburg.