Amathila was born in Fransfontein, Kunene Region. Under the SWAPO Nationhood Programme, she received a scholarship to study medicine in Poland and graduated from the Warsaw Medical Academy in 1969, becoming Namibia's first female doctor. At SWAPO's 1969 Consultative Congress in Tanzania, she became Deputy Secretary for Health and Welfare on the SWAPO Central Committee and Director of the SWAPO Women's Council. She later worked in SWAPO refugee camps. Immediately prior to independence, she was a SWAPO member of the Constituent Assembly, which was in place from November 1989 to March 1990, and since independence in March 1990 she has been a member of the National Assembly of Namibia. She was Minister of Regional and Local Government and Housing from March 21 1990 to September 12 1996, at which point she became Minister of Health and Social Services, serving in that position until becoming Deputy Prime Minister on March 21 2005.
Amathila received the Ongulumbashe Medal for Bravery and Long Service in 1987, and she was the 1991 recipient of the Nansen Refugee Award. In September 1999, she was elected for a one-year term as Chairperson of the World Health Organization's Regional Committee for Africa, and on May 15 2000 she elected as the President of the 53rd Session of the World Health Assembly.
She received the tenth highest number of votes—363—in the election to the Central Committee of SWAPO at the party's August 2002 congress.
Amathila is the wife of politician Ben Amathila.