Mendocino County wine is an appellation that designates wine made from grapes grown mostly in Mendocino County, California. The region is part of the larger North Coast AVA and one of California's largest and most climatically diverse wine growing regions. Mendocino County is one of the northernmost commercial wine grape regions in the state with two distinct climate zones separated by the Mendocino Range. As of 2024, twelve American Viticultural Area (AVA) have been designated within Mendocino County. Mendocino is one of the leading wine growing regions for organically produced wine grapes. Nearly 25% of the cultivation in Mendocino County is grown organically. In 2004, the residents of the county voted to become the first GMO-free county in the United States in an initiative that was supported by many of the county's largest wineries. The county's widespread focus on organic viticulture has inspired journalists to describe it as "California's organic wine Mecca".

The name "Mendocino" comes from the family name of Mendoza in honor of the 16th century Spanish explorer Lorenzo Suárez de Mendoza, 4th conde de la Coruña who explored the Mendocino coast line and his cousin, Antonio de Mendoza the first viceroy of New Spain. The first vineyards in Mendocino were established in the 1850s in the Redwood Valley by returning farmers who failed to find their wealth and prosperity during the California Gold Rush. Most of these winery operations stayed small and were completely eradicated by the enactment of Prohibition in the United States in the early 20th century. With the commercial production of wine banned, vineyards were ripped out and replaced with tree nut and fruit orchards.

The oldest continually operating commercial winery in Mendocino County is Parducci Wines founded in 1931 while Prohibition was still in place. Parducci remained the only commercial winery in Mendocino until the late 1960s. Part of this was due to the relative isolation of the region from the major wine market and business center of San Francisco (more than a 100 miles/160 km to the south), which was so pivotal to the development of the wine industries in nearby Napa and Sonoma County. In 1968, Fetzer Vineyards was founded and would eventually grow to be the largest wine producers in the county. Fetzer would also become a leader in steering the viticultural practices of the county towards more sustainable agriculture and organic wine production. Today nearly 25% of all the vineyards in the Mendocino County are certified organic by the California Certified Organic Farmers-the largest percentage of any county in the state of California.

In 1971 wine production started in the Anderson Valley region. Approximately half of the wine brands produced in Mendocino County are now based in this Western AVA within Mendocino County.

Mendocino County has a wide range of viticultural mesoclimates that are influenced by the county's diversity in climatic and geography. On the eastern borders of the county is the Mayacamas Mountains separating it from nearby Lake County and the influences of the large Clear Lake. Within the county, the Mendocino Range segment of the larger California Coast Ranges essentially divides the region into two climatic spheres. The land to the west of the ranges, closest to the coast tend to have more maritime climate that includes more cooling and rain influences from the Pacific Ocean. Among the wine regions in this cooler area are the Mendocino Ridge, the Anderson Valley and the Yorkville Highlands AVAs. East of the ranges, the climate turns warmer and more Mediterranean around Ukiah and along the path of the Russian River as it makes its way southward to Sonoma County. Among the Mendocino wine regions in this warmer area are the Redwood Valley, Potter Valley, Cole Ranch, McDowell Valley, Covelo, Dos Rios AVAs as well as most of the large general area Mendocino AVA. In this eastern region, the ranges serve as a type of rain shadow and barrier to the cool Pacific fog which leaves the climate during the growing season much drier and warmer with ratings of Region III and IV on the Winkler scale.

In the west, the Pacific fog plays a dominant role in the climate of the Anderson Valley. Following the path of the Navarro River from the Pacific, the fog drifts in and blankets the valley with low hanging cool air. Vineyards in these areas are often planted with cool-climate varieties like Pinot noir, Chardonnay, Gewürztraminer and Riesling. At high elevations in Anderson Valley and nearby Mendocino Ridges beyond the fog's reach, these warmer pockets of lands will usually be planted with more warm climate varieties like Zinfandel. With the nearby Pacific bringing in a steady stream of moisture, rain during the harvest months can be an issue in this part of the county.

Around Ukiah, in the center of the large Mendocino AVA to the east of the Mendocino Ranges, the climate can get very warm to hot during the growing season with mean July temperatures during the peak ripening month often in excess of 73 °F (23 °C). The average annual rainfall of 38 inches (970 mm) is mostly consolidated in the winter months, which means that drought is a common viticultural hazard that often requires supplemental irrigation. The warm allows this part of the county develop full bodied and very ripe red wines from Cabernet Sauvignon, Merlot, Petite Sirah and Zinfandel.

The vineyard soils of the region are mostly deep alluvial soils. Near the Russian and Navarro Rivers, the soil becomes more gravelly-loam while the vineyards planted on the surrounding slope contain more thin scree. North of Ukiah and to the west, vines are often planted with an eastward orientation while further south in Mendocino Valley, vineyards are often planted with a westward orientation in order to prevent heat stress. In general the climate in Mendocino county promotes a shorter growing season of around 268 days compared to the 308 days that is an average growing season in neighboring Sonoma.