In prehistoric times, the valley was inhabited by the Patwin Native Americans, with possible habitation by Wappo tribes in the northwestern foothills.

Their food consisted of wild roots, acorns, small animals, earthworms, grasshoppers, and bread made from crushed California buckeye kernels.

[11] In 1776, a fort was erected by the Spanish Governor, Felipe de Neve, a short distance northwest of Napa, on an elevated plateau.

Following his marriage to General Vallejo’s niece Maria Guadalupe Soberanes, Edward Turner Bale became a citizen of Mexico and was granted Rancho Carne Humana in the northern end of the valley.

Colonel Joseph B. Chiles a guide for one of the earliest immigrant trains to California, was granted Rancho Catacula in 1844.

Following the event of the Mexican–American War, Bear Flag Revolt in 1846 and the Mexican Cession in 1848, settlers were granted deeds from the original ranchos during the 1850s through 1870s.

Descendants of George Yount and Captain Edward Bale played key roles in the early development of Napa County.

Charles Krug, a fellow Prussian compatriot and pioneer viticulturalist at Sonoma, married Lolita's younger sister Caroline with a dowry that included land near the Bale mill.

[15] The county's population began to grow in the mid-century as pioneers, prospectors, and entrepreneurs moved in and set up residence.

Robert Louis Stevenson's book The Silverado Squatters provides a snapshot of life and insight into some of the characters that lived around the valley during the later part of the 19th century.

Stevenson, accompanied by his new bride Fanny Vandegrift and her 12-year-old son from a previous marriage, Lloyd Osbourne, spent the late spring and early summer of 1880 honeymooning in an abandoned bunk house at a played-out mine near the summit of Mount Saint Helena.

In the book, Stevenson's descriptive writing style documented his ventures in the area and profiled several of the early pioneers who played a role in shaping the region's commerce and society.

The resorts became very popular with San Franciscans anxious to escape the cold and foggy weather that often plagues the city to enjoy the warmer climate Napa County offered.

In the mid-1860s, entrepreneur Samuel Brannan purchased land in the northern end of the valley at the foot of Mount Saint Helena and founded Calistoga.

He also founded the Napa Valley Railroad Company in 1864 to bring tourists to Calistoga from San Francisco ferry boats that docked in Vallejo.

This helped to soften the blows to the agricultural economy caused by the phylloxera infestation in the county's vineyards and upcoming prohibition that crippled the wine industry, but resulted in a boom for shipping grapes to immigrant, home winemakers across the country.

[18] The prisoners were utilized to supplement a dwindled able bodied agricultural labor force caused by the needs of the American war effort.

While vineyards were planted on well over 90% of the agricultural land in the county, by the end of the 20th century, modern day farmers have recently begun exploring the possibility of raising other food crops in order to again diversify and take advantage of growing conditions.

[19] At 3:20 a.m. on August 24, 2014, the area was struck by a magnitude 6.0 earthquake centered 3.7 miles (6.0 km) northwest of the city of American Canyon.

[22] In October 2019, heavy smoke and unscheduled black outs by Pacific Gas and Electric Company of up to 20,000 customers affected the county due to fierce winds and threats from the Kincade Fire.

At the north end of Napa County, in the Mayacamas Mountains, lies Mount Saint Helena, the Bay Area's second tallest peak at 4,344 feet (1,324 m) and home to Robert Louis Stevenson State Park; Snell Valley is also situated in northern Napa County; the Missimer Wildflower Preserve is within Snell Valley.

Napa County is home to a variety of flora and fauna including numerous rare and endangered species such as Tiburon Indian paintbrush and Contra Costa goldfields.

On November 4, 2008, Napa County voted 56 percent against Proposition 8, which amended the California Constitution to ban same-sex marriages.

Several still exist in the valley including Charles Krug Winery, Schramsberg, Chateau Montelena, Nichelini and Beringer.

But for many Italian and Swiss families as farm labourers in the vineyards, Prohibition offered the unique opportunity for the growing and shipping of grapes to immigrant home winemakers across the country.

The Mondavi family came West from the Minnesota ore country to Lodi to ship grapes to the "Italian Club" miners.

Giannini, founder of Bank of America in San Francisco, started to promote to rebuild the commerce of wine and viticulture.

In 1965, Napa Valley icon Robert Mondavi broke away from his family's Charles Krug estate to found his own.

Today Napa Valley features more than four hundred wineries and grows many different grape varieties including Cabernet Sauvignon, Chardonnay, Merlot, Zinfandel, and other popular varietals.

In 1968 vintners and civic leaders in the county seized an opportunity to preserve farmland by taking advantage of the Williamson Act[54] enacted by the California Legislature to give landowners property tax relief for designating their land for agricultural purposes.