At first he studied at the Barvinkove elementary school, then realschules of the cities Izium, from which he was expelled for revolutionary activities, and Kursk, which he graduated from in 1890.

While studying at Saint Petersburg State Institute of Technology in 1901, he was arrested on political charges, prompting him to become a full-time revolutionary.

During this exile, he fled to the city of Krasnoyarsk, where he conducted the election campaign of the RSDLP to the Second State Duma of the Russian Empire.

In 1913, Skrypnyk was an editor of the Bolsheviks' legal magazine Issues of Insurance and in 1914 was a member of the editorial board of the Pravda newspaper, while also working for Iskra.

In July 1914, he was arrested again, sentenced to administrative exile in the city of Morshansk, Tambov Governorate, where he worked as an accountant in a Morshanska bank.

After the February Revolution, Skrypnyk was amnestied by the Provisional Government and moved to St. Petersburg (then called Petrograd), where he was elected as a secretary of the Central Council of Factories Committees.

On March 3, 1918, he was elected president of the Secretariat, replacing Yevhenia Bosch, daughter of a German immigrant, who had resigned in protest against the Treaty of Brest-Litovsk.

Skrypnyk was a leader in the so-called Kyiv faction of the Ukrainian Bolsheviks, the independentists, sensitive to the issue of nationality, and promoting a separate Ukrainian Bolshevik party, while members of the predominantly Russian Katerynoslav faction preferred joining the All-Russian Communist Party in Moscow, according to Lenin's internationalist doctrine.

He returned to Ukraine, where he was a special commissioner of the Defense Council for combating the insurgent movement and led the suppression of the rebellion of Danylo Terpylo.

He worked for this cause with almost obsessive zeal and, despite a lack of teachers and textbooks and in the face of bureaucratic resistance, achieved tremendous results during 1927–29.

As Soviet industrialization and collectivization drove the population from the countryside to urban centres, Ukrainian started to change from a peasants' tongue and the romantic obsession of a small intelligentsia into a primary language of a modernizing society.

Skrypnyk convened an international Orthographic Conference in Kharkiv in 1927, hosting delegates from Soviet and western Ukraine (former territories of Austria-Hungary, then part of the Second Polish Republic).

The conference settled on a compromise between Soviet and Galician orthographies, and published the first standardized Ukrainian alphabet accepted in all of Ukraine.

He gave public testimony against "nationalist deviations" such as writer Mykola Khvylovy's literary independence movement, political anticentralism represented by former Borotbist Oleksandr Shumsky, and Mykhailo Volobuiev's criticism of Soviet economic policies which made Ukraine dependent on Russia.

His first wife, Maria Skrypnyk (maiden name Mezhova; 1883–1968) was a Bolshevik from pre-revolutionary times, a member of the Krasnoyarsk organization of the RSDLP, where they met.