Defeat for Hertha marks a disappointing start to life at the helm for new coach Lucien Favre, who will have to cope this season without the likes of Yildiray Basturk, Kevin-Prince Boateng and Dick van Burik, who all left the club over the summer.
Frankfurt's Sotirios Kyrgiakos had the first chance of the game on 12 minutes, his header from six yards sailing just over Jaroslav Drobny's crossbar.
Eight minutes later the hosts were at it again, this time Alexander Meier sending a header crashing in on goal but Drobny gathered with ease.
And after dominating proceedings for the opening spell, Frankfurt got their reward on 30 minutes as Amanatidis converted with the hosts' third headed opportunity of the match, the Greece international nodding the ball beyond Drobny and into the top right-hand corner.
A disappointing second period produced little in the way of chances for either side.
The game opened up a little in the closing minutes, however, with Hertha's best chance of the game coming with a 73rd-minute Carlos Lucio free-kick that brought a smart stop from Frankfurt custodian Markus Proll.
Frankfurt had two chances to put the game to bed in the final 10 minutes as first Meier and then Albert Streit went close, but against a toothless Hertha attack, the hosts' lead never looked in danger of being relinquished.
Frankfurt: Proell-Kyrgiakos,Ochs,Russ,Spycher-Inamoto,Fink-Mahdavikia,Meier,Streit,Amanatidis