Charles Davenport was made director of the Station for Experimental Evolution while retaining his directorship of the Biological Laboratory. In 1904, Davenport hosted a ceremony to mark the opening of the Station for Experimental Evolution at Cold Spring Harbor. By 1905, the Main Building of the Station for Experimental Evolution was completed. A stucco finish overlaid the brick construction of the Main Building in the style of other libraries built by the Carnegie Foundation during this time. The building was equipped with rooms for insects, birds, and aquatic animals, as well as rooms for breeding canaries. Research rooms and a Library were also located in the Main Building. Many scientists worked in the building, including George Shull, a maize geneticist who came to the Station for Experimental Evolution in 1906. He grew an experimental crop of maize in the field next to the Main Building and described the occurrence of "hybrid vigor" in corn.

By 1911, the Main Building was no longer used for breeding animals. It was predominantly used for research and storage.