Goals from Jan Polak and Diego silenced a sell-out Waldstadion crowd, but as the home team's fans awaited agonisingly for news of Hamburg's game against Bayer Leverkusen, Alexander Meier gave them hope with a penalty.
A Ricardo Rodriguez own goal in the last minute then brought the Eagles level and earned them a place in the Europa League as Hamburg succumbed against Leverkusen.
Wolfsburg had to play for 55 minutes of the game with 10 men after Makoto Hasebe was shown the red card for giving away the penalty.
Wolfsburg arrived in Frankfurt with nothing to play for other than to prove their recent upsurge in form, which may have come too late to help them challenge for a place in Europe, was still no coincidence.
Against a nervous-looking Frankfurt, it did not take long for Dieter Hecking's side to stamp their authority on the game.
Polak raced in to head Rodriguez's corner in unchallenged to give them the lead in the eighth minute.
Vieirinha hit the post as Wolfsburg nearly scored a second, but Takashi Inui also hit the woodwork at the other end as Frankfurt responded.
However, on the break, Wolfsburg grabbed a second with Diego providing a cool finish to Ivica Olic's cross.
Diego nearly scored a third before Hasebe fouled his compatriot Inui to earn a red card in the 35th minute.
Meier stepped up to score his 16th goal of the season and bring Frankfurt back into the game.
With Hamburg's game against Leverkusen still finely poised at 0-0, Frankfurt knew that a goal for the northerners in that match would deprive them of a place in Europe and they came out stronger in the second half.
Marco Russ thought he had brought them level after Anderson's effort came back of the post, but he was in an offside position.
Yet they had to wait until the very last minute of the game, once Leverkusen had already taken the lead against Hamburg, before celebrating their berth in Europe next season.
Pirmin Schwegler's pass was headed into his own goal by Rodriguez to let the celebrations begin in earnest for Frankfurt.