A five-minute spell in the first half decided the game in Frankfurt's favour, with Alexander Meier putting them in front before Josue was sent off and Takashi Inui added a second.
With only 10 men, Wolfsburg were unable to find a response as Frankfurt controlled proceedings to move on to 30 points at the halfway stage of their first season back in the top flight following a year in the second division.
Bas Dost could have given the story a different beginning but he lacked the courage to shoot in the ninth minute with only Kevin Trapp to beat, choosing instead to pass to Diego, who was unable to reach the ball.
His unwillingness to shoot typified Wolfsburg's day and was in stark contrast to Frankfurt, who took the lead through Meier in the 12th minute from a free-kick.
Pirmin Schwegler gave the prolific midfielder another chance to demonstrate his strength in the air, and he nodded in his 11th goal of the season to top the league's goalscoring charts.
Four minutes later, the day took another turn for the worse for the Wolves when Josue was shown a straight red card for a foul on Olivier Occean.
Two minutes after that, the game was effectively over when Inui was left in space to touch in Stefan Aigner's cross as the Wolfsburg defence fell to pieces.
Naldo managed to get in a leg to prevent Sebastian Jung from making it three five minutes before half-time, with the home side happy to hear the whistle at the end of a 45 minutes to forget.
It did not get much better in the second half for Lorenz-Gunther Kostner's side either, although Frankfurt showed them a little mercy with a more restrained approach.
They never looked in any danger of conceding, though, and created a few chances to score a third with Schwegler hitting a direct free-kick just over the crossbar.