Discovery of the Drosophila Bithorax complex and elucidation of its function. Lewis founded the field of developmental genetics and laid the groundwork for current understanding of the universal, evolutionarily conserved strategies controlling animal development.

In 1995 Lewis shared the Nobel Prize in Physiology or Medicine with Christiane Nüsslein-Volhard and Eric E. Wieschaus "for their discoveries concerning the genetic control of early embryonic development."