Shenderovich was born in Moscow into a family of Belarusian Jewish origin. In 1980, he graduated from the Moscow State Art and Cultural University, specializing in "direction of volunteer theatrical groups". He is best known as a scriptwriter of popular political puppet show Puppets, which was aired on NTV 1994 to 2002. He hosted satirical author program Total on NTV 1997 to 2001 and TV-6 in 2002. Later, Shenderovich ran a weekly program Processed Cheese on the Echo of Moscow radio station. The texts of this program's editions were later collected in his book Better Two Heads Than One, implying Russian President Dmitry Medvedev and Prime Minister Vladimir Putin. Nowadays Shenderovich is a columnist of The New Times, a liberal Russian weekly.
He is known as an outspoken critic of Vladimir Putin's rule and the government's stance on the war in Chechnya. Shenderovich is among the 10 first signatories of the online anti-Putin manifesto "Putin Must Go" published in March 2010. On 26 December 2010, Shenderovich played a major role in organizing a "Moscow for Everyone" (Russian: Москва для всех) rally in the capital of Russia, in response to race riots having occurred earlier in the month.
On 30 December 2021, Russia's Ministry of Justice added Shenderovich to its list of “foreign agents”.
On January 11, 2022, Shenderovich left Russia because of a pressure campaign against him by officials, including his controversial designation as a "foreign agent."He was living in Poland as of January 13, 2022.