Archaeological evidence indicates the island has been a site of human activity since the Early Woodland period, around 1000 BC.

A characteristic type of pottery known as Selden Island ware dates from this period.

[1] It is also the site of a significant Late Woodland period settlement known as the Walker Prehistoric Village, which was added to the National Register of Historic Places in 1975.

[2] In 2002, following the diagnosis of two Loudoun County teenagers with malaria, mosquitoes from the island were found to carry the Plasmodium vivax malarial parasite.

[3] In 2004, Selden Island was purchased by the Howard Hughes Medical Institute as an addition to the Janelia Farm Research Campus.