In 2001, he staged his first production in Moscow. Serebrennikov has staged drama productions in Moscow Chekhov Theatre, Latvian National Theatre, Theatre of Nations. He has been active in opera staging productions for the Mariinsky Theatre, and the Bolshoi Theatre in Russia, where he has also been a stage director and a designer for a ballet, Komische Oper Berlin and Stuttgart Opera in Germany.

Serebrennikov is one of the artistic directors of Territory Festival in Moscow. Since 2008 he is a professor of the Moscow Art Theatre School, where he has a class of actors and directors. His productions have been presented at the Wiener Festwochen, and the Avignon Theatre Festival. His films have been screened at Cannes Film Festival, Locarno Film Festival, Rome Film Festival, and the Warsaw International Film Festival where his film Yuri's Day received the Grand Prix.

In 2012, he was appointed artistic director of The Gogol Center.

On May 23, 2017, Serebrennikov's apartment and the Gogol Center facilities were raided by law enforcement agencies in connection with an alleged embezzlement at the Seventh Studio, a non-profit organization established by Serebrennikov.

While no charges against Serebrennikov have been filed, some of Russia's most prominent cultural figures saw the publicized raid of his apartment as a political gesture, discouraging Serebrennikov and others from criticizing the government. (Serebrennikov had criticised the 2014 Russian annexation of Crimea and has spoken out in support of Russia’s LGBT community.) Vladimir Urin, and Yevgeny Mironov, among others, in May 2017 expressed their support of Serebrennikov in a letter passed on to Russian President Vladimir Putin at a public function.

On August 22, 2017, Serebrennikov was detained by the Investigative Committee of Russia, suspected of masterminding a fraud scheme involving a state subsidy the Seventh Studio received from the government of Russia from 2011 to 2014.

According to a source cited by Interfax, in the case of “Gogol-center” the alleged theft of 2014 budget funds caused damage to the state valued at several million dollars. Other sources say a total of just over one million rubles. Serebrennikov has been placed under house arrest until October 19. Seventh Studio former director Yuri Itin has already been placed under house arrest since May 31, 2017. Ex-chief accountant of Seventh Studio, Nina Maslyaeva, gave confessions and has been held in custody since then.