Ihlas Bebou played a starring role as Axel Bellinghausen and Rouwen Hennings gave the hosts a 2-0 lead at the break.
Hennings added a second after the restart and Arianit Ferati also scored in what was a very promising performance at the ESPRIT arena.
There was just one change made by Friedhelm Funkel, as Özkan Yildirim came in for the suspended Kevin Akpoguma; a move which saw Kaan Ayhan drop into midfield.
For Rüdiger Rehm, it was a case of wholesale change. Steffen Lang, Andreas Voglsammer, Manuel Prietl and Leandro Putaro were brought in after the defeat to Würzburger Kickers, with Tom Schütz, Christoph Hemlein, Brian Behrendt and Manuel Junglas all on the bench.
Bellinghausen and Hennings have Fortuna ahead at the break
The game began slowly with both sides trying to keep possession; Fortuna were happy to come forward on the ball while Bielefeld prefered to hit the hosts on the break. They had the first real opening of the tussle when Sebastian Schuppan's free-kick was met by Julian Börner, but was cut-out by an alert Robin Bormuth almost immediately.
It was still a tough watch up to the 20-minute mark as Funkel marched to the edge of his technical area to gee his men up. That worked a treat as a ball into Hennings didn't stick and a mix up from Malcolm Cacutalua and Stephan Salger in midfield saw Bebou produce a clever flicked pass to play in Bellinghausen who passed past the oncoming Wolfgang Hesl into the bottom corner.
Fortuna continued to come forward from that point and almost had a second before Börner made a vital intervention to block Yildirim's shot. Bebou's effort from the well-worked resulting corner was stopped at the near post by a rocking Bielefeld defence that were struggling to recover from the opening blow.
A second goal would come when Lukas Schmitz's wicked cross towards Hennings saw Börner get a little too tight and bring his man to the floor. Christian Dietz sent the centre-back off for his second booking in five minutes, and Hennings dusted himself off to send Hesl the wrong way from the penalty spot.
Bielefeld put up some resistance towards the break but were twice denied at the back post as Ayhan and Jerome Kiesewetter both kept out the visitors with important blocks. There were changes late in the first half for both teams as Junglas replaced Putaro to bolster the midfield, while Kiesewetter replaced Bellinghausen.
Brilliant Bebou stars in the second half
To their credit, the half-time break saw Bielefeld come into the game with renewed energy in a bid to try and get a foothold with 10 men. Unfortunately for them, a combination of stoic defending and Michael Rensing's smart save from Voglsammer at his near post meant that they were still chasing two goals.
Fortuna were keen to wake from their slumber and the fans raising of the noise levels helped them do just that. Some neat play through the middle saw Bebou spin his man and go through on goal, only to be denied by Hesl. The ball fell perfectly for Ferati, who had came on just one minute before, to sweetly strike through the bodies and in.
Bebou was truly a handful for the visiting back-line and Hesl was again called into action, while a curling effort went narrowly wide moments later. The Togo international would have his hand in the fourth and final goal of the game, which saw him collect a cross, turn and fire towards the back post for Hennings to slide in for his brace.
The final stages provided little in the way of excitement, though Hemlein brought a good save from Rensing at the death. Bielefeld now sit bottom on goal difference and could fall further behind should the sides above them pick up results this weekend. Fortuna, on the other hand, are now just three post away from an automatic promotion spot.