Graduated in 1891 from University of Toronto and became a fellow in zoology at Clark University. In 1892 he was lured by President Harper to the newly founded University of Chicago. In 1894 (at the age of 24) he received the degree of Doctor of Philosophy in Zoology. Between 1894-1899 he was instructor of zoology at University of Michigan. Between 1899-1900 he was Professor of Biology at Vassar College but in 1900 he was called back to Chicago as Assistant Professor of Zoology. In 1906, at the age of 36, he became professor of Embryology. In 1910 he succeeded C.O. Whitman as chairman of the Department of Zoology and continued in that capacity until 1931. From 1931 to 1935 he was Dean of the Division of the Biological Sciences.
He was Director of the Woods Hole Marine Biological Laboratory from 1908-1939.
He founded and was first President (1930-1939) of the Woods Hole Oceanographic Institution.
His most important academic work--as distinct from his considerable contributions to the institutions of science in America--included experiments on the phenomenon of freemartin in cattle, which led to his discovery of the existence, and analysis of, the operation of the male hormone.
FR Lillie Road in Woods Hole as well as the Lillie building at the MBL are named after him.