Mabel Gillespie was born in St. Paul, Minnesota on 13 October 1894. She was educated at Radcliffe College in Massachusetts. Inspired by the work of Jane Addams and Hull House she became involved in progressive politics.

In 1912 Gillespie was appointed to the Minimum Wage Commission established in Massachusetts. Five years later she became the president of the Stenographers' Union. The following year she joined the Woman's Trade Union League, serving on its executive board from 1919 until 1922.

A member of the Democratic Party, she was the first woman to take the oath of office as state representative in January, 1925. She felt that the legislature should seek fewer, better laws, and introduced one bill in first term, providing increased state funding of bridges. She was a strong supporter of a bill to extend water mains in small towns, believing that this would be a great boon to women. She lost her seat in 1937.

Mabel Gillespie died on 24 November, 1982.