Born at Yelets in Oryol Governorate, she began acting at an amateur theatre club in the Siberian city of Tomsk.
There she worked on stage with such actors as Maria Yermolova, Elena Gogoleva, Aleksandra Yablochkina, Vera Pashennaya, Alexander Yuzhin, Alexander Ostuzhev, Vladimir Davydov, Konstantin Zubov, Stepan Kuznetsov, Nikolay Annenkov, Mikhail Tsaryov, Igor Ilyinsky and many other notable Russian actors.
She became famous in 1902 after her powerful stage performances as Korobochka in Nikolai Gogol's classic drama Dead Souls.
Then she worked with director Yakov Protazanov in the first Russian sci-fi experiment, Aelita (1924), where she appeared alongside Mikhail Zharov and Igor Ilyinsky among other fellow actors from the Maly Theatre.
Varvara Massalitinova was designated as a People's Artist of the RSFSR and was awarded for her performances on stage and in film (Stalin Prize, 1941).