In 1995, Nikolayev became a member of the board of the open joint-stock company Almazergienbank, a commercial bank based in Yakutsk.

[4] From 1997 to 2002, he was a deputy of the second convocation of the upper chamber of the State Assembly of the Sakha Republic from the Olenyoksky District.

On 2002, he was appointed as a deputy of the 3rd convocation of the State Assembly of Yakutia from the Union of Right Forces party, till 2004.

In January 2012, Aysen Nikolayev was nominated by the United Russia party as a candidate for the mayoral elections in Yakutsk.

[8] On 28 May 2018, by the Decree of the President of Russia Vladimir Putin, Nikolayev was appointed as the acting Head of the Sakha Republic.

Since July 2022, against the backdrop of the Russian invasion of Ukraine, he has been under sanctions of the British government because he "manages a regional state body of the Russian Federation, which supports or implements actions or policies that undermine or threaten the territorial integrity, sovereignty and independence of Ukraine.

"[12][13] In December 2022, the Office of Foreign Assets Control of the United States Department of the Treasury added Nikolayev and 28 other governors of the federal subjects of Russia to the Specially Designated Nationals and Blocked Persons List due to their involvement in the enforcement of the conscription of Russian citizens in response to the mobilization order in September 2022.