The first chance of the game fell the way of the home side, although Elias Kachunga failed to make the most of the opening from close range when he fired wide of the target.
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Chances proved to be few and far between in the remainder of the first half, with Alexander Maier eventually making the breakthrough shortly before the hour when he unleashed a shot beyond Lukas Kruse via the post.
The lead lasted for just eight minutes, though, as Marvin Ducksch latched onto a ball inside the area before firing into the top corner of the net.
Takashi Inui and Haris Seferovic both had the chance to retain the Eagles' lead, although a mixture of good defending and solid goalkeeping ensured that the game remained level heading into the final 15 minutes.
The missed opportunities proved costly, with Uwe Hunemeier edging Paderborn ahead for the first time courtesy of a composed finish beyond Mario Vrancic, and Stefan Kutschke reacted quickest shortly after to put the game beyond doubt when he fired home goal number three for the hosts.
Frankfurt, who came into today's encounter on the back of a four-game unbeaten run, drop down to eighth in the Bundesliga table, while Paderborn climb above their opponents into seventh place.