She was born in Brooklyn, New York on November 11, 1846.

Though Green's book The Leavenworth Case is frequently cited as the first mystery written by an American woman, The Dead Letter by Seeley Regester was published earlier (1866).

Green is credited with shaping detective fiction into its classic form, and developing the series detective. Her main character was detective Ebenezer Gryce of the New York Metropolitan Police Force, but in three novels he is assisted by the nosy society spinster Amelia Butterworth, the prototype for Miss Marple, Miss Silver and other creations. She also invented the 'girl detective': in the character of Violet Strange, a debutante with a secret life as a sleuth. Indeed, as Journalist Kathy Hickman writes, Green "stamped the mystery genre with the distinctive features that would influence Writers from Agatha Christie and Conan Doyle to contemporary authors of suspenseful "whodunits". In addition to creating elderly spinster and young female sleuths, Green's innovative plot devices included dead bodies in libraries, newspaper clippings as "clews", the coroner's inquest, and expert witnesses. Yale Law School once used her books to demonstrate how damaging it can be to rely on circumstantial evidence. Written in 1878, her first book, The Leavenworth Case: A Lawyer's Story, sparked a debate in the Pennsylvania State Senate over whether the book could "really have been written by a woman".

On November 25, 1884, Green married the actor and stove designer, and later noted furniture maker, Charles Rohlfs (1853 – 1936), who was seven years her junior. Rohlfs toured in a dramatization of Green's The Leavenworth Case. After his theater career faltered, he became a furniture maker in 1897, and Green collaborated with him on some of his designs. Together they had one daughter and two sons: Rosamund Rohlfs, Roland Rohlfs, and Sterling Rohlfs. Her daughter Rosamund married Robert Twitty Palmer. She died in 1935 and was buried in Buffalo, NY where her grave is today located in the Forest Lawn Cemetery.

Room Number 3, and Other Detective stories,(1905), featuring:

The Golden Slipper, and Other Problems for Violet Strange, (1915), featuring:

Green died on April 11, 1935 in Buffalo, New York, at the age of 88.

In a discussion of women Writers of detective fiction, scholar Ellen Higgins in 1994 chronicled the work of Green as popularizing the genre a decade before Arthur Conan Doyle brought out his first Sherlock Holmes story. "I only found out afterward that some people were a little upset with it because they don't want to hear about women competing with the master", Higgins said.

In 2002, Buffalo Literary Walking Tours began an annual series of weekend walking tours highlighting authors with local connections. Green is included along with Mark Twain, F. Scott Fitzgerald, Herman Melville, Taylor Caldwell, and others.

Green was in some ways a progressive woman for her time—succeeding in a genre dominated by male writers—but she did not approve of many of her feminist contemporaries, and she was opposed to women's suffrage.