Born at Darmstadt, Kekulé studied at the universities of Erlangen under Karl Friederichs, and at Berlin under Eduard Gerhard, Johann Gustav Droysen, and August Böckh.
In 1889 Kaiser Wilhelm II of Germany personally requested Kekulé to be the antiquities director of the collections in Berlin.
In the following year, he succeeded Carl Robert at the university in Berlin which he held jointly with the directorship.
Kekulé greatly increased the size of the imperial collections through a combination of astute buying and commissioning excavations, assisted in the latter by Theodor Wiegand.
He eschewed Jahn's "monumental philology" and classification for a methodology closer to Brunn, mixed with an esthetic sensitivity akin to J. J. Winckelmann.