Vynnychenko was born in Yelisavetgrad (Kirovohrad), the Kherson Governorate of the Russian Empire, in a family of peasants. His father Kyrylo Vasyliovych Vynnychenko earlier in his life was a peasant serf that moved from a village to the city of Yelisavetgrad where he married a widow Yevdokia Pavlenko. From her previous marriage Yevdokia had three children: Andriy, Maria, and Vasyl, while from the marriage with Kyrylo only one son Volodymyr. Upon graduating from a local public school the Vynnychenko family managed to enroll Volodymyr to the Yelyzavetgrad Male Gymnasium (today is the building of the Ukrainian Ministry of Extraordinary Situations). In later grades of the gymnasium he took part in a revolutionary organization and wrote a revolutionary poem for which was incarcerated for a week and expelled from school. That did not stop him from continuing his studying as he was getting prepared for his test to obtain the high school diploma (Matura). He successfully passed the test in the Zlatopil gymnasium from which obtained his attestation of maturity.

In 1900 Vynnychenko joined the Revolutionary Ukrainian Party (RUP) and enrolled in the law department at Kiev University, but in 1903 he was expelled for participation in revolutionary activities among the Kievan workers and peasants from Poltava and jailed for several months in Lukyanivka prison. He managed to escape his incarceration. Afterward, he was forcibly drafted into the Russian tsarist army, where he began to agitate soldiers with revolutionary propaganda. Tipped off that his arrest was imminent, Vynnychenko fled to Western Ukraine, Galicia, a region that was part of the Austro - Hungarian Empire. When trying to return to Russian Ukraine in 1903 with revolutionary literature, Vynnychenko was arrested and jailed in Kiev for two years. After his release in 1905, he passed his exams for a law degree in Kiev University.

In 1905 Vynnychenko became a founding and leading member of the Ukrainian Social Democratic Worker's Party, which was affiliated with the Russian Social Democratic Party and led by Martov & Lenin. In 1906 Vynnychenko was arrested for a third time, again for his political activities, and jailed for a year; before his scheduled trial, however, the wealthy patron of Ukrainian literature and culture, Yevhen Chykalenko, paid his bail, and Vynnychenko fled the Russian Ukraine again, effectively becoming an emigre writer abroad from 1907 to 1914, living in Lemberg (Lviv), Vienna, Geneva, Paris, Florence, Berlin. While abroad, Vynnychenko married Rosalia Lifshitz, a Russian Jewish doctor. From 1914 to 1917 Vynnychenko lived near Moscow throughout much of WWI and returned to Kiev in 1917 to assume a leading role in Ukrainian politics.

After the Russian revolution in February 1917, Vynnychenko served as the head of the General Secretariat, a representative executive body of the Russian Provisional Government in Ukraine. He was authorized by the Central Rada of Ukraine (a de facto parliament) to conduct negotiations with the Russian Provisional Government, 1917.

Vynnychenko resigned his post in the General Secretariat on August 13 in protest for the government of Russia declining the Universal of Central Rada. For a brief period he was replaced by Dmytro Doroshenko who composed a new government the next day, yet unexpectedly he submitted his resignation as well on August 18. Vynnychenko was invited to return, form a cabinet and redesign the Second Universal to petition a federal union with the Russian Republic. His second government was confirmed by A. Kerensky on September 1.

It is often claimed that political mistakes of Vynnychenko (who was, in effect, prime minister) and Mykhailo Hrushevsky (the head of the Central Rada) cost the newly established Ukrainian People's Republic its independence. Both men were strongly opposed to the creation of the army of the Republic and repeatedly denied the requests by Symon Petliura to use his volunteer forces as the core of a would-be army (Polubotok Regiment Affair).

After the October Revolution and the Kiev Bolshevik Uprising many of his secretaries resigned after the Central Rada disapproved the Bolsheviks actions in Petrograd with the ongoing confrontations in Moscow as well as the other cities in the country (Odessa Soviet Republic). On January 22, 1918, the Ukrainian People's Republic has proclaimed its independence due to the Bolshevik intervention headed by the Russian minister Antonov - Ovseyenko. The country was squeezed between the abandoned German - Russian front lines to its western border and the advancing Bolshevik forces of Muravyov along the eastern border. Within days, Mikhail Muravyov manage to invade Kiev forcing the government to evacuate to Zhytomyr whose retreat was secured by the great efforts of the Sich Riflemen. During the evacuation the Ukrainian government managed to secure military assistance in the face of the Central Powers. The government of the Ukrainian People's Republic signed a highly criticized treaty with the Germans to repel the Bolshevik forces in exchange for a right to expropriate food supplies. That treaty also required the Russian SFSR to recognize the Ukrainian People's Republic. Around that time the Vynnychenko's government established an economic agreement with the government of Belarus People's Republic through the Belarus Chamber of Commerce in Kiev. Alas, Vynnychenko's was replaced as well by the Socialist - Revolutionary government of Vsevolod Holubovych.

After the coup d'etat of Hetman Skoropadsky (in collaboration with Germans) in March, 1918, Vynnychenko left Kiev. Later after forming the Directorate of Ukraine he took an active part in organizing a revolt against the Hetman. The revolt was successful and Vynnychenko returned to the capital on December 19, 1918. The Directorate, a temporary central executive committee, proclaimed the restoration of the Ukrainian People's Republic. The Directorate was put in charge until the Ukrainian Constituent Assembly would convene to elect a permanent body of government.

Vynnychenko, unable to restore order and overcome the disagreement among the Directors, stepped down on February 11, 1919. He emigrated the following March.

While in emigration, Vynnychenko wrote Rebirth of a Nation (Вiдродження нацiї, 1919), an account of the Ukrainian revolution up to that point. He argued that the Ukrainian nationalists had made mistakes by ignoring the social question, and that the Bolsheviks had similarly failed to see the importance of national liberation. However, he concluded that the Bolsheviks were beginning to change their position on the Ukrainian nation. For this reason, he began to support reconciliation with the Bolsheviks and returned to Ukraine.

He formed the Foreign Group of the Ukrainian Communist Party, which was mainly made up of other former members of the Ukrainian Social - Democratic Party, in order to promulgate this position. In June 1920 Vynnychenko himself travelled to Moscow in an attempt to come to an agreement with the Bolsheviks. After four months of unsuccessful negotiations, Vynnychenko had become disillusioned with the Bolsheviks: he accused them of Great Russian Chauvinism and insincerity as socialists. In September 1920 he emigrated again, and revealed his impressions of Bolshevik rule. This split the Foreign Group of the Ukrainian Communist Party: some remained pro-Bolshevik and indeed returned to Soviet Ukraine; others supported Vynnychenko, and with him conducted a campaign against the Soviet regime in their organ Nova doba ("New Era").

Vynnychenko spent the following thirty years in Europe, residing in Germany in the 1920s, then moving to France. As an émigré, Vynnychenko resumed his career as a writer; in 1919 his writings were republished in an eleven volume edition in the 1920s. In 1934 Vynnychenko moved from Paris to Mougins, near Cannes, on the Mediterranean coast, where he lived on a homestead type residence as a self-supporting farmer and continued to write, notably a philosophical exposition of his ideas about happiness, Concordism. Vynnychenko called his place Zakoutok. He died in Mougins, near Cannes, France in 1951. Rosalia Lifshitz after her death passed the estate to Ivanna Vynnykiv - Nyzhnyk (1912 – 1993), who emigrated to France after the World War II and lived with the Vynnychenkos since 1948.