The excavations in 1977 in the South of Focșani determined that the actual hearth of the city has been inhabited since the Neolithic period, the objects discovered there belonged to Criș culture (c. 5000 BC). There was discovered a Dacian treasure III-II BC, a treasure trove of Roman imperial coins, other proofs of the material culture of the Carps and the Sarmatians from II-III Century AD. The invasion of the Goths, Huns, Slavs, and Tatars had a harsh impact on the territory where the city is located today.

First documented mention of the city was in the 16th century (January 30, 1575, when Alexander Voda of Wallachia mentioned in a document that he had been struck "with deceit in Focșani by Ioan Voda"), Milcov settlement is much older. Until the early 17th century, Focșani was recorded as a village, and after 1615-1620 was mentioned the name of fair, over time, becoming the most important settlement between Trotuș and Râmnicu Sărat, laying at the junction of the trade roads which connect Wallachia with the countries of Western and Eastern Europe.

The first document which mentioned the existence of people from Focșani, was issued by the Hospodar of Wallachia, Alexandru II Mircea. Royal Charter, written in January 1575, refers to a battle fought in 1572, the year in which Focșani is mentioned for the first time in a document.
Due to the fact that "Focșanii" were right on the border which separated Moldavia from Wallachia, in course of time, two cities with the same name where formed: Focșanii Wallachia and Focșanii Moldavia.

Around 1641, on an anonymous stranger traveler described Focșanii as a great city situated, "right on the border between Moldavia and Muntenia, separated by a brook, rather a moor, over which is built a stone bridge". The brook was actually a backwater created by diverting a part of Milcov’s waters, which at first had enough water to put in motion a windmill, but which after 1831 was almost completely closed.

On January 1, 1848 the customs between Moldavia and Wallachia was suppressed, thus Focșani lost its function as customs. After the election of Alexander John Cuza as a Ruler of both Principalities, he issued a decree on 10th of July 1862, which legislated as follows "both parts the city Focșani, this side and across Milcov River, will unify into a single city, which will be the Municipality of Putna County." Between 1859 and 1862, in Focșani functioned a Central Committee tasked with drawing up the common laws of the two Principalities, the Court of Cassation for two Prefectures (Putna and Râmnicu Sărat), two courthouses, two police units, two sections of the city.Flag of the civil guard Focsani.

The period from Unity to independence, is known as a period of prosperity. In 1866 was built the Secondary School, known today as "Unirea" National College, in 1867 the County and Municipal Hospital and in 1873 the Public Garden. The late 19th century and early 20th century, the city witnesses a flourishing development, in such a way that the several institutions are formed, such as the Philharmonic Society, symbolically named „Doina Vrancei” (1907), the Public Library (1912), 'Mr. Gh. Pastia' Theatre (inaugurated in 1913), the Palace of Justice.On December 30, 1881, Focşani hosted the First Zionist Congress. On September 8, 1917, in Focșani was signed the Armistice between the representatives of the Romanian Army and the Central Powers.
During the interwar period continues the development of the city Focșani by building an electric plant, the People’s Athenaeum "Maior Gheorghe Pastia", the National Bank building, built in a neoclassical architectural style, the Telephones Palace; it improves the network of the water supply and street network, the Heroes’ Mausoleum Focsani was built between the years 1924 and 1926 and the Monument of the Heroes of Regiment 10 Dorobanți built in1930.

In the interwar period the exacerbation of the right-wing politics starts an anti-Semitism manifest against the Jewish community existing in the city. Thus, in 1925, Corneliu Zelea Codreanu's marriage with Elena Ilinoiu (the ceremony was officiated in Focșani) has also a political importance. Anti-Semitic speeches are held and shops of the Jewish community are being destroyed. After 1950, the city witnessed a rapid industrialization process with direct impact on the process of economic growth, the population started a migration to the urban areas and thus its integration in the urban structure of the town:

• The first apartment blocks (Gara Districts, South Districts, Bahne Districts, central area of the city) were built.
• The industrial area starts a gradual development
• A textile factory was built (currently SC Incom SA), wood processing plant (1963) (SC Mopaf SA), plant for devices, stamping, molding and splitting machines (1971) (SC Romseh SA), the electric apparatus company (SC Instaelectric SA), wine production and commercialization (S.c. Vinicola S.a., S.C. Vincon S.A.), plastics manufacturing plant (1974) (Uniplast R-Ltd. (1973), enameled pots manufacture (1979) (SC VEF SA) metallurgical plant (Metanef), units belonging to the light industry (S.C. Heim-MIlcov SA), cotton-spinning mill (1981), EFECTOFIL SA (1991)), as well as food industry plants (milk, meat, vegetables and fruits processing) having been built in this period.

The city of Focsani became the Municipality of Vrancea County, in 1968, with the new administrative territorial organisation of Romania.