Pamfilova started her career on the central repair and engineering works in Moscow as an engineer. She went on to become a People's Deputy of the USSR and member of Supreme Soviet of the USSR.
During the period 1991 until 1994, she led The Ministry of Social Care under President Boris Yeltsin. Between 1994 and 1999, Pamfilova was elected three times as member of the RussianDuma.
In 2000 she was the first woman to run as a candidate in a Russian presidential election campaign. However, she faced stiff competition from Yabloko leader Grigory Yavlinsky for the liberal vote, and her share of the vote was very low.
Since 2004 she has been a head of Vladimir Putin's Human Right Commission.
At a State Duma session of October 7, 2009 a MP from United Russia, Robert Shlegel, proposed that the president dismiss Pamfilova from the Human Rights Commission for advocating Alexandr Podrabinek’s rights. The watchdog, led by Pamfilova, had called the protests “a persecution campaign … organized by irresponsible adventurists from Nashi” and said the activists were showing open signs of extremism.