Kai Simons is the son of a physics professor. His father convinced him to study medicine, though he originally wanted to study physics. While studying at the University of Helsinki, Simons spent a summer internship in the Stockholm laboratory of Bengt Samuelsson There, he studied mechanisms of vitamin B12 absorption. He worked with other students to organize a campaign to fight taeniasis, a disease common in eastern Finland where eating raw fish is popular.
After completing his MD in 1964, he began a postdoctoral fellowship at Rockefeller University in New York City where he worked between 1966 and 1967 on blood serum protein polymorphism. He returned to Helsinki in 1967, where he began working as a Junior Investigator for the Finnish Medical Research Council at the University of Helsinki. He became a group leader in 1972 and was a biochemistry professor in 1971–79 at the medical faculty of this university At first, he continued his work on serum proteins. Next, together with Leevi Kääriäinen and Ossi Renkonen, he started a research team – later joined by Ari Helenius, his first PhD student and later a post doctoral researcher who became Simons' brother-in-law. After a one-month stay in MRC Laboratory for Molecular Biology in Cambridge, the group started investigating a Semliki Forest virus, introduced to Simons by Kääriäinen.
In 1975 Simons came to Heidelberg (Germany), as one of the EMBL group leaders. Together with Ari Helenius he helped to develop EMBL, headed at this time by John Kendrew. In years 1982–1998 Simons was a coordinator of the Cell Biology Program there. During this time he for the first time presented the concept of lipid rafts.
In 1999 he took part in setting up ELSO (later incorporated into EMBO), which later he presided over.
He was one of the initiators of establishing and building Max Planck Institute of Molecular Cell Biology and Genetics in Dresden (Germany), where he moved. Formally from 1998 (beginning of MPI-CBG construction) and practically from 2000 he was one of five institutes directors and also a group leader there Since 2006 he is a director emeritus'.
In 2012 he started-up a biotech company Lipotype GmbH, where he is a CEO.
He is married to Carola Simons and a father of three: twins – Mikael (neurobiologist) and Katja (sociologist), and the youngest of three, Matias (physician).