Born in Brooklyn, New York, Green had an early ambition to write romantic verse, and she corresponded with Ralph Waldo Emerson. When her poetry failed to gain recognition, she produced her first and best known novel, The Leavenworth Case (1878), praised by Wilkie Collins, and the hit of the year. She became a bestselling author, eventually publishing about 40 books.

She 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.

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.

Green married the actor, and later designer and artist, Charles Rohlfs on November 25, 1884. Seven years her junior, Charles was made to give up acting by Anna's father before he could marry her. They had one daughter and two sons, Roland Rohlfs and Sterling Rohlfs, who were test pilots. Green died in Buffalo, New York, at the age of 88.