Prelog’s potential for natural sciences became apparent already at the age of 15, when he published his first scientific paper as a high school student, with the help of his professor. He obtained a doctoral degree in chemistry in Prague, and, in 1935, accepted the position of lecturer in organic chemistry at the Technical Faculty of the University of Zagreb, where he modernised the course. He contributed to the advancement of the Croatian pharmaceutical industry, while a group of his students and scientific associates within the so-called Prelog Zagreb School of Organic Chemistry became recognizable in Europe.

After the outbreak of World War II, at the invitation of Leopold Ružička, he moved to Zurich to work at the Organic Chemistry Laboratory of the Federal Polytechnic School (Eidgenössische Technische Hochschule, “ETH”). After Ružička retired in 1957, he succeeded him as head of the Laboratory.

Although Prelog was a scientist with a wide array of interests, the focus of his work was on stereochemistry (the study of the spatial arrangement of atoms in molecules). In 1975, he received the Nobel Prize in Chemistry for his research and contribution to this field.