Hertha were unchanged from their opening day 4-1 win over Werder Bremen, whereas Stefan Ilsanker and Almamy Toure came in as Frankfurt's two changes from their draw against Arminia.
A substitution as early as the 15th minute forced Frankfurt into an early change as Steven Zuber replaced Filip Kostic, who was removed after picking up an injury.
This did not seem to affect the visiting side at all as Andre Silva stepped forward from the penalty spot on the half-hour mark to tuck in the opener after he had gone down in the six-yard area.
Hertha looked to hit back immediately after a ball from Maximilian Mittelstadt picked out Dodi Lukebakio, who unfortunately failed to get the better of Frankfurt goalkeeper Kevin Trapp.
These turn of events spurred on their counterparts nine minutes to halftime as Bas Dost showed up in the area to head home Daichi Kamada's delivery following a well-worked set-piece.
Soon after halftime, Hertha missed a golden chance to get back into the game when Mittelstadit again drew blanks from a promising position following a set-play.
This followed another missed opportunity on 58 minutes as Lukebakio failed to turn home from yet another set piece scenario orchestrated by the hosts.
Following a steady spell either side, Frankfurt bagged a third inside the last 20 minutes after Kamada teed-up Sebastian Rode to apply a left-footed finish outside the box.
Hertha were handed a chance to stage a comeback on 77 minutes when Martin Hinteregger slotted the ball into his own net after attempting a defensive clearance.
Nothing of the sort materialised for the home side, who suffered their first defeat of the season while Frankfurt picked up their first win this term.