In 1714, he set out to seek his fortune in Russia, and unsuccessfully solicited a place at the offices of Princess Charlotte of Brunswick-Lüneburg, wife of the Tsarevich Alexei Petrovich.

Later, during his patron's absence, Biron, a handsome, insinuating fellow, succeeded in supplanting him in Anna's favour, and even procuring the disgrace and banishment of Bestuzhev and his family.

In 1723, Biron married Benigna Gottlieb von Trotha genannt Treyden (1703–1782), lady-in-waiting to Regent Anna and the daughter of a Baltic-German nobleman.

At Anna's coronation (19 May 1730), Biron was appointed grand chamberlain, made a count of the Empire, and granted an estate at Wenden with an income of 50,000 crowns a year.

His ascendancy over the empress was unshakable, and whenever required, Biron's enemies and rivals were swept out of the way quite literally; he is said to have caused over 1000 executions, while the number of persons exiled by him to Siberia is estimated at between 20,000–40,000.

Nevertheless, he showed himself an administrator of considerable ability, and maintained order in the Empire at a time when troubles could have been expected, because the main Romanov line was now extinct, and even the empress did not have children or definite heirs.

Still, it was found necessary to supply large sums of money, smuggled into Courland and Semigallia in the shape of bills payable in Amsterdam to bearer, in order to persuade the electors to fall in with Anna's choice.

The Emperor Charles VI, subordinating everything to his Pragmatic Sanction, readily countenanced these violent acts, and the king of Prussia was bought by certain territorial concessions.

On her deathbed, very unwillingly and only at his urgent entreaty, Anna appointed Biron regent during the minority of the baby emperor, Ivan VI of Russia.

Her common sense told her that the only way she could save the man she loved from the vengeance of his enemies after her death was to facilitate in time his descent from his untenable position.

[citation needed] Finally, on 26 October 1740, a so-called "positive declaration" signed by 194 dignitaries, in the name of the Russian nation, conferred the regency on Biron.