Siegfried Hekimi was born in Zürich and obtained his undergraduate degree in Biology at the University of Geneva. He did not immediately pursue graduate studies but instead engaged in a full-time career as a cyclist, first as a member of the amateur Swiss National Team and then as a professional in various teams in Switzerland and Italy. He was selected for the World Championships four times and participated in such well known races as the Tour de France and the Giro d'Italia. After this adventure he completed a PhD in Neurobiology in 1988 with Professor Michael O'Shea, again at the University of Geneva. His thesis focused on the biosynthesis of neuropeptides, which was poorly understood at the time.

It was to tackle this problem that he first developed an interest in using invertebrate models to study evolutionarily conserved processes. This approach led him to study the cardiac bodies of locusts, a pair of endocrine glands almost completely dedicated to the production of the peptidic adipokinetic hormones. He then moved to the famed Laboratory of Molecular Biology (LMB) of the Medical Research Council in Cambridge, UK, to collaborate with Dr J.G. White as a post-doctoral fellow of the Swiss National Science Fund. It is at the LMB that Sydney Brenner developed the nematode Caenorhabditis elegans as one of the premier research tools in genetics, and where Hekimi developed his interest for using 'the worm' for translational studies in the biology of aging. It is also in Cambridge that he identified the first mutants that helped to demonstrate that aging could be manipulated genetically and that inducing mild mitochondrial dysfunction could in fact slow down the aging process of animals. After three years in Cambridge, Hekimi joined the Department of Biology at McGill University.