Wilson, born the son of a judge in Geneva, Illinois, was educated at Yale and Johns Hopkins where, in 1881, he gained his PhD. After further training abroad at Cambridge, Leipzig, and Naples he returned to America and taught for some years at the Massachusetts Institute of Technology and Bryn Mawr College. In 1891 Wilson moved to Columbia where he spent the rest of his career, serving as professor of zoology from 1894 until his retirement in 1928.

In his Cell Development and Inheritance (1896) Wilson stressed the importance of the cell theory, hoping that its application to the problems of development and heredity would lead to advances in these areas. He did important work on the concept of cell lineage, studied internal cellular organization, and investigated the part played by the chromosomes in the determination of sex. It was in Wilson's department that the science of genetics really became established through the work of T. H. Morgan and Hermann Muller.