For at least 3,000 years these hills were the hunting grounds and summer home of the native Ohlone people. During the dry season they left their permanent settlements along the bay shore for seasonal hunting camps near upland creeks and streams. Deadfall and pit traps plus arrows and spears provided grizzly and venison steaks to supplement the abundant fish and oysters found in the bay.
In 1833 the Mexican governor of Alta California granted 4,400 acres of land above Los Trancos and San Francisquito creeks to Domingo Peralta and Don Maximo Martinez. This was the beginning of Rancho del Corte Madera.
After a Martinez daughter married into the Boronda family, the property became known as Boronda Farm. A stockbroker who bought the land from the Borondas in 1914 planted fruit trees and other exotic species in what is now the Orchard Glen Picnic Area.
Dr. Russel V. Lee, a founder of the Palo Alto Medical Clinic, bought the property in 1941 and built an A-frame barn and stable, now the Nature Interpretive Center. In 1958 he sold 1,194 acres to the City of Palo Alto for $1,000 an acre, with the intention of preserving the land for open space. Estimated value of the land at that time was $3,000 an acre. In effect, Russel Lee and his wife gave more than a $2 million gift to the city.
Foothills Park was opened to residents of Palo Alto in 1965.
On November 3, 2020, the Palo Alto City Council voted to abolish the residents-only policy. Effective December 17, 2020, Foothills Park was open to the public.
On February 22, 2021, the Palo Alto City Council voted to change the name of Foothills Park to Foothills Nature Preserve.