[2] In the early 2000s, Vladimir Mashkov starred in several Hollywood films: Dancing at the Blue Iguana (2000), 15 Minutes (2001), An American Rhapsody (2001) and Behind Enemy Lines (2001).

[2] Mashkov played the Russian millionaire Platon Makovsky, whose prototype was Boris Berezovsky, in Pavel Lungin's 2002 drama Tycoon.

The next year, he appeared on television as merchant Rogozhin in the adaptation of Fyodor Dostoyevsky's novel The Idiot, directed by Vladimir Bortko.

In 2004, he appeared in the role of director, screenwriter and producer of the film Daddy based on Alexander Galich's play The Sailor's Silence, in which he also starred Abram Schwartz.

[2] He starred in the 2005 adaptation of Boris Akunin's novel The State Counselor, next year he played in the action movie Piranha and the US television series Alias.

[2] In 2007, Vladimir Mashkov played detective David Gozman in the historical crime series Liquidation[2] He portrayed the character of a hired killer in the 2008 film The Ghost.

In 2011, Vladimir Mashkov appeared in the American blockbuster Mission: Impossible – Ghost Protocol, where he played Russian agent Sidorov.

The disaster film Flight Crew by Nikolai Lebedev premiered in 2016, where Mashkov played experienced pilot Zinchenko.

On 18 March 2022, Mashkov spoke at Vladimir Putin's Moscow rally commemorating the annexation of Crimea from Ukraine and supporting the Russian invasion.

[12] In 2024, a Ukrainian court sentenced Mashkov in absentia to ten years in prison for war propaganda and for encouraging the violation of Ukraine's territorial integrity.

[13] Mashkov claims he was in discussions with Rockstar Games to voice the character of Niko Bellic in Grand Theft Auto IV and that the character's appearance is based on him, specifically from his role of the Tracker in the 2001 movie Behind Enemy Lines, but he ultimately turned down the offer.