Born on August 13, 1857, in New Haven, Connecticut to Irish immigrants from Tipperary, Thomas J. and Bridget (Lundigan) Quinlan, Mary Ellen grew up in a comfortable home in Cleveland, Ohio, where her father, Thomas, prospered as a local businessman and real estate investor. Her family moved to Cleveland, Ohio, where her father started his own business in stationery supplies, dry goods, candies, tobacco and liquors. Quinlan had done so well, he was able to provide his children a sound education, and music lessons. Mary Ellen attended the Ursuline Academy on Euclid Avenue. At 15, she attended St. Mary's Academy and graduated with honors in music, playing Chopin's Polonaise for piano, op. 22, at the commencement. 
Ella met James O'Neill at her father's house. Quinlan's store was less than two blocks from the Cleveland Academy of Music, a flourishing hall where the dashing James O'Neill began appearing as early as 1870. Ella developed a crush on the 26 year old actor. O'Neill left Cleveland for a theater company in Chicago, but met Ella again a few years later. Thomas J. Quinlan died on 25 May 1874 of tuberculosis at age 41. On June 14, 1877 Ella married James in St. Ann's Church on East 12th St. in Manhattan, despite her mother's concern that her sheltered and refined daughter would not be happy as the wife of a touring actor.
Almost immediately Ella had to contend with a lawsuit against her husband from a former mistress who claimed James was the father of her son. The scandal devastated her. Many years later, long after her death, her son Eugene O'Neill, in his play Long Day's Journey Into Night created a character who represents his mother. The character Mary Tyrone bemoans her lonely life: "I've never felt at home in the theater. Even though Mr. Tyrone has made me go with him on all his tours, I've had little to do with the people in his company, or with anyone on the stage."
Ella was on tour with James in San Francisco when in September 1878, her first son, James Jr., was born in the house of one of the actor's friends.
A second son, Edmund Burke O'Neill was born in 1883, in a St. Louis hotel, the young family again on the circuit. In late winter 1885 Ella left her sons with her mother in New York to join her husband on the road in Denver. While she was away, her older son contracted measles, a highly contagious disease. Edmund then also fell ill with the measles and died. Ella blamed James Jr., believing that he purposely exposed his brother to the disease. Ella would never get over the guilt she associated with this "desertion"; nor would she ever conquer an irrational resentment toward her first born. Her surviving son was sent to boarding school, and she vowed not to have another child. She did, however, when Eugene was born in October 1888.
In October, 1888, in order to relieve the pains of the difficult birth of her third son, Eugene Gladstone O'Neill, Ella was administered morphine by the attendant physician. This was the beginning of a longtime addiction to the drug. When he was a teenager, Eugene walked in on his mother giving herself an injection. Later her husband was afraid to leave her alone when they traveled together on tour. He brought her to the theater with him, where she sat in his dressing room in a drug-induced stupor.
Early in 1914, Ella went through a cure, and this time remained free for the rest of her life. In April, 1919, she underwent a mastectomy for breast cancer. When her husband died in August 1920, Ella handled his financial affairs, selling their cottage in New London, Connecticut, which was the setting for Long Day's Journey Into Night. While on a trip to California with her son Jamie, Ella took ill and was diagnosed with a brain tumor. She died on February 28, 1922.
Ella O'Neill later became the model for Mary Tyrone in Eugene O'Neill's final work Long Day's Journey Into Night, which tells the story of the Tyrone family, who closely resemble the members of Eugene's family. This character says the famous line, "Something I need terribly. I remember when I had it I was never lonely nor afraid. I can't have lost it forever, I would die if I thought that. Because then there would be no hope."
- Shaughnessy, Edward L., "Ella O'Neill and the Imprint of Faith", The Eugene O’Neill Review, Suffolk University, 1992
- Shaughnessy, Edward L., "Ella, James, and Jamie O'Neill: 'My Name Is Might-Have-Been'", The Eugene O’Neill Review, Suffolk University, 1991
- "Eugene O'Neill", American Experience, PBS
- "James O'Neill", History of the San Francisco Theatre Vol. XX, WPA, Northern California, 1942
- Black, Stephen A., "Mrs. O'Neill's Illness", New York Theater wire