Ethel Lilian Boole was born in Ireland on May 11, 1864, to the mathematician, George Boole, and the feminist philosopher Mary Everest, who was the niece of George Everest and a writer for Crank, an early-20th-century periodical.

Voynich was a significant figure not only on the late Victorian literary scene but also in Russian émigré circles. In 1902 Boole married Wilfrid Michael Voynich, a Polish revolutionary, antiquarian, and bibliophile, the eponym of the Voynich manuscript.

She is most famous for her novel The Gadfly, first published in 1897 in the United States (June) and Britain (September), about the struggles of an international revolutionary in Italy. This novel was very popular in the Soviet Union and was the top bestseller and compulsory reading there, and was seen as ideologically useful; for similar reasons, the novel has been popular in the People's Republic of China as well. By the time of Voynich's death The Gadfly had sold an estimated 2,500,000 copies in the Soviet Union and was made into a movie in 1928 in Soviet Georgia (Krazana) and in 1955.

In 1955, the Soviet director Aleksandr Fajntsimmer adapted the novel into a film of the same title (Russian: Ovod). Composer Dmitri Shostakovich wrote the score (see The Gadfly Suite). Along with some other excerpts, the Romance movement has since become very popular. Shostakovich's Gadfly theme was also used in the 1980s, in the BBC TV series Reilly, Ace of Spies. In 1980 the novel was adapted again as a TV miniseries The Gadfly, featuring Sergei Bondarchuk as Father Montanelli.

According to the British journalist Robin Bruce Lockhart, Sidney Reilly — a Russian-born adventurer and secret agent employed by the British Secret Intelligence Service (BSIS) — met Ethel Voynich in London in 1895. Lockhart, whose father, R.H. Bruce Lockhart, was an agent of the BSIS and knew Reilly, claims that Reilly and Voynich had a sexual liaison and voyaged to Italy together. During their romance Reilly is said to have "bared his soul to his mistress", and revealed to her the story of his strange adventures in South America. After their brief affair, the story goes, Voynich published The Gadfly, whose central character Arthur Burton was based on Reilly. Lockhart cites no evidence for any of his claims. Andrew Cook, an historian and noted biographer of Reilly, convincingly refutes Lockhart's account. He suggests instead that Reilly may have been reporting on Voynich and her political activities to William Melville of the Metropolitan Police Special Branch. There is, in fact, no evidence that Reilly ever met Ethel Voynich or her husband Wilfrid.