In 1840 he began studying philology in Leipzig with Moriz Haupt and Gottfried Hermann, among others, which he continued from 1843 at the University of Berlin, among others with Karl Lachmann .
He received his doctorate in Berlin in 1846 with the thesis De supplementis commentariorum C. Julii Caesaris and then worked as a private scholar in Leipzig.
In 1854 Nipperdey was appointed full professor, on January 13, 1855, a member of the university's senate and in the summer semesters 1857 and 1861 dean of the faculty of philosophy.
In 1867, Nipperdey took over the professorship of eloquence from Karl Wilhelm Göttling, but had been relieved from holding ceremonial speeches in Latin.
Nipperdey fell ill with a nerve and spinal cord disease, which got progressively worse; in January 1875 he died by suicide.