Nathan Ake was taken off the pitch on a stretcher after sustaining a serious injury on international duty.
Tijjani Reijnders got the hosts off to a perfect start in Amsterdam before Deniz Undav equalised to put Germany back on level pegging.
With the Dutch looking to restore their lead on the brink of the interval Ake pulled up with what appeared to be a hamstring strain as he attempted to control the ball in the opposition half.
The severity of the situation was immediately apparent as the referee waved over the medical team to attend to 29-year-old.
The Manchester City defender was distraught as he removed from the pitch on a stretcher in the Netherlands' clash with Germany
After initially attempting to return to his feet, a clearly emotional Ake was then removed from the pitch on a stretcher and replaced by Arsenal's Jurrien Timber.
Joshua Kimmich then gave Julian Nagelsmann's the lead before half-time before Denzel Dumfries made it 2-2.
Ake's injury will come as a headache for Pep Guardiola, as his side face a busy fixture schedule following the international break.
The Premier League champions will look to continue their perfect start to the season when they play host to Brentford on Saturday.
Then just four days later they get their European campaign underway at home to Inter Milan in the revamped Champions League.
Arsenal then visit the Etihad in a game that could prove to have significant implications on the title race come the end of the season.