She was born as Ella Alexander on July 26, 1858 in Van Wert, Ohio. Boole's father was a prominent Lawyer, who edited a free soil newspaper and supported reforms during Reconstruction following the Civil War. She attended public schools in Van Wert, then the College of Wooster where she studied classics. She had an aptitude for natural science and developed skills in public speaking. She received an A.B. degree (1878), followed by an A.M. degree (1881).

Boole's husband was active in prohibition and temperance activities, in which she joined him. Boole joined the Women's Christian Temperance Union (WCTU) in 1883. She showed great skill as an organizer of new unions, and became vice-president of the New York state union in 1891. After the death of Boole's husband, she was able to support her family through an inheritance from her father and income from her speaking engagements and temperance activities. In 1898, she became President of the New York WCTU. She held this position until 1925, with the exception of a six-year period when she was corresponding secretary of the Woman's Board of Home Missions of the Presbyterian Church (1903-1909). One of her key activities was in shifting WCTU work away from its emphasis on collecting petitions, and towards direct lobbying of legislators.

Following the enfranchisement of women in the United States, Boole decided to run for office herself. In 1920, she unsuccessfully challenged James Wolcott Wadsworth Jr. for the Republican Party nomination for the United States Senate. After losing the nomination, she ran as a candidate for the Prohibition Party against Wadsworth and the Democratic and Socialist Party candidates in the general election. Wadsworth won easily with 52% of the vote, while Boole came in third place with 7% of the vote, not far ahead of the Socialist candidate.

Boole served as head of the national Woman's Christian Temperance Union from 1931 to 1947. She died on March 13, 1952 at age 93.