[2]: 2 It was in 1921 that, at the age of 15, and with his teacher’s help, he published a short communication entitled »Eine Titriervorrichtung« (Preparation for Titration) in the prestigious German journal »Chemiker-Zeitung«.

In addition to my routine studies, I have enrolled as an extramural student in the crafts school and I spend whole afternoons three times a week learning how to file, hammer and do all the other things that an eager young locksmith should know.

Following his father's wishes, he moved to Prague, where he received his diploma in chemical engineering from the Czech Technical University in 1928.

His teacher was Emil Votoček, while his assistant and mentor Rudolf Lukeš introduced him to the world of organic chemistry.

[citation needed] Prelog wanted to work in an academic environment, so he accepted the position of lecturer at the University of Zagreb in 1935.

In 1941, while at Zagreb, Prelog developed the first synthesis of adamantane, a hydrocarbon with an unusual structure that was isolated from Moravian oil fields.

With Ružička's help, he gained support from CIBA Ltd. and started to work in the Organic Chemistry Laboratory in the Swiss Federal Institute of Technology (ETH, or Eidgenössische Technische Hochschule).

He found an ideal topic in the elucidation of the structure of solanine; he continued his work on Cinchona alkaloids and started to investigate strychnine.

Later he worked on elucidating the structures of aromatic Erythrina alkaloids with Derek Barton, Oskar Jeger and Robert Burns Woodward.

Recognizing the growing importance of microbial metabolites, Prelog started working on these compounds, which possess unusual structures and interesting biological properties.

[4]: 580 In 1944 at the ETH, Prelog managed to separate enantiomers with "asymmetric" trivalent nitrogen by column chromatography at a time when this method was still in its infancy.

His work on medium-sized alicyclic and heterocyclic rings established him as a pioneer in stereochemistry and conformational theory and brought an invitation to give the first Centenary Lecture of the Chemical Society in London in 1949.

He synthesised medium-sized ring compounds with 8 to 12 members from dicarboxylic acid esters by acyloin condensation and explained their unusual chemical reactivity by a "nonclassical" strain because of energetically unfavorable conformations.

[4]: 580–581 In his research of asymmetric syntheses, Prelog studied enantioselective reactions and established rules for the relationship between configuration of educts and products.

[13] Prelog was elected a Foreign Member of the Royal Society (ForMemRS) in 1962 for his contribution to the development of modern stereochemistry.

[11] An intellectual with a wide cultural background, Prelog was one of the 109 Nobel Prize winners who signed the peace appeal for Croatia in 1991.