Archaeological evidence suggests that the earliest known production of wine, made by fermenting grapes, took place from the late Neolithic or early Chalcolithic, possibly as early as the sixth millennium BC, between the Caucasus and the Middle East, with evidence of winemaking at different sites dated from 6000 BC in Georgia, 5000 BC in Iran, and 4100 BC in Armenia. During an extensive gene-mapping project in 2006, archaeologists analyzed the heritage of more than 110 modern grape cultivars, narrowing their origin to a region in Georgia, where wine residues were also discovered on the inner surfaces of 8,000-year-old ceramic storage jars. Chemical analysis of 7,000-year-old pottery shards indicated early winemaking in the Neolithic village of Hajji Firuz Tepe in Iran's Zagros Mountains. Other notable areas of wine production have been discovered in Greece and date back to 4500 BC. The same sites also contain the world's earliest evidence of crushed grapes. A winemaking press found in 2011 in the Areni-1 site of Armenia has been dated to around 4100 BC.

However, the spread of wine culture westwards was most probably due to the Phoenicians who were centered on the coastal strip of today’s Lebanon – itself one of the world’s oldest sites of wine production. The wines of Byblos were exported to Egypt during the Old Kingdom (2686 BC–2134 BC) and throughout the Mediterranean. Evidences include two Phoenician shipwrecks from 750 BC discovered by Robert Ballard, whose cargo of wine was still intact. As the first great traders of wine ('Cherem'), the Phoenicians seem to have protected it from oxidation with a layer of olive oil, followed by a seal of pinewood and resin - this may well be the origin of the Greek retsina.

Literary references to wine are abundant in Homer (8th century BC, but possibly composed even earlier), Alkman (7th century BC), and others. In ancient Egypt, six of 36 wine amphoras were found in the tomb of King Tutankhamun bearing the name "Kha'y", a royal chief vintner. Five of these amphoras were designated as originating from the king's personal estate, with the sixth from the estate of the royal house of Aten. Traces of wine have also been found in central Asian Xinjiang in modern-day China, dating from the second and first millennia BC.

The first known mention of grape-based wines in India is from the late 4th-century BC writings of Chanakya, the chief minister of Emperor Chandragupta Maurya. In his writings, Chanakya condemns the use of alcohol while chronicling the emperor and his court's frequent indulgence of a style of wine known as madhu.

A 2003 report by archaeologists indicates a possibility that grapes were mixed with rice to produce mixed fermented beverages in China in the early years of the seventh millennium BC. Pottery jars from the Neolithic site of Jiahu, Henan, contained traces of tartaric acid and other organic compounds commonly found in wine. However, other fruits indigenous to the region, such as hawthorn, cannot be ruled out. If these beverages, which seem to be the precursors of rice wine, included grapes rather than other fruits, they would have been any of the several dozen indigenous wild species in China, rather than Vitis vinifera, which was introduced there some 6,000 years later.

 

One of the lasting legacies of the ancient Roman Empire was the viticultural foundation laid by the Romans in the areas that today are world-renowned wine regions. In places with garrison towns (e.g. Bordeaux, Trier, and Colchester), the Romans planted vineyards to supply local needs and limit the cost of long-distance trading. In medieval Europe, the Roman Catholic Church supported wine because the clergy required it for the Mass. Monks in France made wine for years, aging it in caves. An old English recipe that survived in various forms until the 19th century calls for refining white wine from bastard—bad or tainted bastardo wine.