In 1702, Prince Cherkassky held a post of senior stolnik (tsar's personal assistant) and was soon assigned to assist his father, Prince Mikhail Yakovlevich Cherkassky, who had been a voivod in Tobolsk at that time.

During the election of Anna Ivanovna for the Russian throne in 1730, Cherkassky, the richest man in Russia in terms of the amount of serfs he owned at that time, was in charge of the gentry party, which had been in opposition to the verkhovniki (members of the Supreme Privy Council).

For his services to the Crown he was appointed one of the three cabinet ministers and was promoted to the rank of grand chancellor in 1740.

As a cabinet minister, Tcherkassky signed a trade agreement with Great Britain in 1734.

In his post as chancellor, he signed a treaty with Prussia in 1740 and Great Britain in 1741.