He enrolled on 12 September 1692 at Leiden as a student of medicine and graduated on 27 February 1694 with a dissertation De lumbricis ("About earthworms", Ludg.
He succeeded his uncle Jan Commelin, who together with Joan Huydecoper founded the Hortus Botanicus Amsterdam.
Caspar worked on books that were left uncompleted by the death of his uncle, Jan Commelin, and enjoyed the support of Nicolaes Witsen.
Jan Commelin, based his work on the taxonomic system devised by John Ray.
In 1724, Caspar Commelin, while an inspector at the Collegium Medicum, had his portrait painted by Cornelis Troost.