Born into one of South Australia's leading families, Nancy was the second daughter of Edward (later Sir) and Hilda May Holden. Her father is recognised as the primary founder of the Australian car industry. Nancy Holden was educated at Woodlands Church of England Girls' Grammar School, Adelaide, and Camposenea in Paris. She later studied part-time at Adelaide University, as well as working with many charities. On 19th February 1936, Holden married businessman and company director Frank Charles Buttfield and they had two sons.

Her interest in politics was aroused when she joined a Model Parliament that met in the Christadelphian Hall near Holden's city factory. Robert Menzies (later prime minister of Australia) gave her advice about a possible parliamentary career. In 1954 Nancy stood for and won Liberal Party endorsement to challenge for the safe Labor federal seat of Adelaide. Although defeated, she did achieve a 3% swing against Labor.

In 1955 a senate vacancy was created when South Australian Senator George McLeay died suddenly. Buttfield was nominated by State Parliament and became South Australia's first female Member of Parliament, serving as a Senator for 16½ years. As well as serving as a director for the Co-operative Building Society for 30 years, Nancy Buttfield was a Member of the Commonwealth Advisory Council for the Handicapped. She also was vice-president of the Good Neighbour Council, on the Women's Committee of the Queen Victoria Maternity Hospital and co-manager of the Mile End Maternity Hospital.

In their retirement, the Buttfield's set-up a Youth Venture Club, established at their property 'Fairfield' at Chain of Ponds in South Australia, where leadership skills are developed through outdoor activities such as bush walking, horse riding, archery and canoeing. Together they established the Dame Nancy Buttfield biennial prize for decorative arts. The $5000 prize and several scholarships are open to all Australians and all age groups.

Dame Nancy Buttfield died on 4 September 2005.