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The site of the current Fitzgerald Marine Reserve was originally settled by Native Americans approximately 5,800 years ago.
The explorer Gaspar de Portola was visited and was entertained as a guest by local Native Americans in the mid- 18th century on the site.
In 1908, the Ocean Shore railroad extended through the town of Moss Beach, effectively creating the town as a tourist destination.
The site has long been a source of research and materials for marine biologists and collectors, so much so that, in 1969, San Mateo County urged the State of California to designate the site as a state reserve to protect the remaining flora and fauna. On August 5, 1969 the site was officially designated as a state reserve and was named after James V. Fitzgerald.