Two goals apiece for Stefan Kiessling and Andre Schurrle ensured Leverkusen kept pace with second-placed Borussia Dortmund and maintained a six-point cushion over Schalke in fourth to remain on course for a place in the Champions League next season.
An own goal from Daniel Schwaab was all Fortuna had to show for a spirited performance which ended in a crushing defeat and left them still only five points clear of the drop zone.
Leverkusen took the lead when Leon Balogun fouled Sidney Sam inside the penalty area and Kiessling converted from the spot for his 17th goal of the season.
Robbie Kruse and Robert Tesche both went close as Fortuna responded well, getting a deserved equaliser in the 41st minute.
Kruse's low cross was met by Schwaab, who in trying to clear in front of Stefan Reisinger, only managed to turn the ball into his own goal.
The goal gave Fortuna confidence and they took the game to their guests, but like in the first half, it was Leverkusen who took the lead against the run of play.
Sam's shot was deflected out to Schurrle, who drilled the ball in to give Leverkusen the lead in the 62nd minute.
The game remained on a knife-edge until the 84th minute when Kiessling teed up Schurrle to double Leverkusen's advantage and end Fortuna's hopes of finding a second equaliser.
Kiessling round off the win in the 88th minute with his 18th goal of the season after being set up inside the penalty area by Daniel Carvajal.