Wilamowitz-Moellendorff was born in Markowitz (Markowice), a small village near Hohensalza (Inowrocław), in the then Province of Posen (now part of the Kuyavian-Pomeranian Voivodeship), to a Germanized family of distant Polish ancestry.

His father, a Prussian Junker, was Arnold Wilamowitz, of Szlachta origin and using the Ogończyk coat of arms, while his mother was Ulrika, née Calbo.

Here he was educated and learned, amongst the rest, the English language, also studying privately with Dietrich Volkmann, teacher and then Master of the school.

He developed a lifelong rivalry with his fellow student Friedrich Nietzsche and a close friendship with his contemporary Hermann Diels.

Even before he gained a professorial title, Wilamowitz was a member of a scholarly dispute about Nietzsche's Birth of Tragedy that attracted much attention.

When Wilamowitz left Göttingen, he was succeeded by Georg Kaibel, a close associate from his student days and his successor at Greifswald.

In 1897, with the support of his friend Diels, Wilamowitz was offered a position at the Royal Friedrich-Wilhelms-Universität at Berlin, as successor to Ernst Curtius.

Further, Wilamowitz taught as a guest lecturer in Oxford (1908) and Uppsala (1912), was a corresponding member of the Norwegian Academy of Science and Letters (1909) and the Scientific Society of Lund (1921).

During his presidency of the Prussian Academy, Wilamowitz oversaw the continuation of August Böckh's and Adolf Kirchhoff's publication series, the Inscriptiones Graecae.

As a representative of Postclassicism, he concentrated less on literary history but rather aimed to extract biographical information on the respective authors from the preserved texts.

Apart from his seminal general works (Greek Literature from Antiquity, Hellenistic Poetry), he published numerous detailed studies of Euripides, Homer, Aeschylus, Pindar and Aristotle.

In recent decades, the American scholar William M. Calder III has been publishing a series of important documents about and by Wilamowitz, including much of his correspondence with Diels, Eduard Norden, Mommsen, Paul Wendland, and others.