Historically, Tatoosh Island was inhabited seasonally by Makah fishing camps and employees of the United States Coast Guard, Weather Bureau, and Navy.

Tatoosh Island has been home to Cape Flattery Light, which overlooks the entrance to the Strait of Juan de Fuca, since December 28, 1857.

Beginning in 1967, Professor Robert T. Paine of the University of Washington and his colleagues have undertaken detailed studies of marine ecology on the island.

Key ecological concepts explored by this research include keystone species, control by consumers and natural disturbances on ecosystem structure and spatial patterning, species interaction strength, body size-dependent population dynamics, and impacts of environmental changes such as ocean acidification and El Niño events on complex ecosystems.

This is due to its exposed location for maritime winds that temper both heat and cold extremes year-round and eliminate dry summers typical of the western/west-southwestern coast of North America.