Lytvyn started his career at the Kyiv State University (1978−86), then he worked as Head of Directorate in the Ministry of Higher and Secondary Vocational Training of the Ukrainian SSR (1986−89).

During the Cassette Scandal audiotapes were released on which Kuchma, Lytvyn and other top-level administration officials are allegedly heard discussing the need to silence Georgiy Gongadze for his online news reports about high-level corruption.

Lytvyn stated "The investigation confirmed my innocence in this case, despite the fact that efforts have been, are being and will be taken to make me practically the main person accused [of killing the journalist]".

[15][16] In 2002, Lytvyn was elected to Verkhovna Rada as the head of the party bloc For United Ukraine ("Za edynu Ukrainu").

At the parliamentary elections on March 26, 2006, his Lytvyn's People's Bloc won 2.44% of the popular vote and no seats since it did not meet the 3 percent threshold.

Lytvyn's allies (together with other parties) declared the voting results forged, filing a court suit and starting a public campaign.

On December 6, 2009, Mykola Melnychenko, former bodyguard to Kuchma, accused Lytvyn of ordering the murder of journalist Georgiy Gongadze in 2000.

[19] Lytvyn took part in the 2012 Ukrainian parliamentary election as a People's Party candidate in single-member districts number 65 (first-past-the-post wins a parliament seat) located in Narodychi Raion.

[23] In the 2014 parliamentary election Lytvyn was re-elected into parliament as an independent candidate in electoral district 65 located in Zviahel with 41.48% of the votes.

[27] In March 2021 Lytvyn lost in the election for the rector of the Taras Shevchenko National University of Kyiv, taking fourth place with a result of about 4% of the vote.