Although he struggled with academic politics throughout his career and difficult conditions during World War I and II, his work had lasting influences on the fields of phylogenetics, morphology, and embryology.

He graduated in 1908 and went on to pursue a PhD under the guidance of Arnold Lang (1855—1914), a former professor of Jena University and close friend of Ernst Haeckel as well as a long-time associate of Anton Dohrn.

In 1910, Naef accepted a position of a permanent visiting scientist at the Zoological Station, where he began work on a cephalopod monograph that had been started by Giuseppe Jatta.

[2] Nevertheless, he returned to the Naples Zoological Station in 1926 to complete his cephalopod monograph, which was published in two parts in the Station's Fauna und Flora des Golfes von Neapel und der Angrenzenden Meers-Abschitte (Fauna e Flora del Golfo di Napoli) series,[3] which formed the basis for his two short but significant monographs on systematic theory.

He planned a comprehensive Textbook of Vertebrate Zoology, but his work on the project was stifled by isolating governmental regulations during World War II.

[1][2] Along with his mentors and peers, Naef readily accepted Darwin's theory of descent with modification, and embraced the challenge of understanding evolutionary relationships among organisms.

[6] Naef expressed it so: "For decades, phylogenetics lacked a valid methodological basis and developed on the decayed trunk of a withering tradition rooted in the idealistic morphology and the systematics of pre-Darwinian times.

There was talk of systematic 'tact' and morphological 'instinct', terms which were felt rather than understood and consequently insufficient to form the frame of a science which required sound definitions and clearly formulated principles.

Towards the end of his career, Naef published several detailed accounts of Systematische Morphologie,[7][8] including a succinct summary in the widely read 2nd edition of the Handwörterbuch der Naturwissenschaften.

[9] This work strongly influenced Willi Hennig, who developed a similar philosophy but disagreed with Naef on the primacy of direct observation in favor of pursuing the metaphysical "true nature" of phylogenetics.