By 1870 more than 200,000 copies of her works which ranged from biographies of saints to pamphlets on social issues had circulated throughout the world, the proceeds from which went towards victims of the Famine of 1879 and helping to feed the poor.

When she was a teenager, her parents separated, and she, her mother, and brother Samuel went to live with her grand-aunt in Exeter, Devon, where Margaret attended boarding school.

Influenced by the Oxford Movement, and motivated by the sudden death of her fiancé, Charles Holmes, in 1852 she joined a convent of Puseyite Anglican nuns.

In 1861 she was sent with a small group of nuns, led by Mary O'Hagan to Kenmare, County Kerry, then one of the most destitute parts of Ireland, to establish a convent of Poor Clares.

[2] She wrote 35 books, including many popular pious and sentimental texts on private devotions (A Nun's Advice to her Girls), poems, Irish history and biography, founding Kenmare Publications,[5] through which 200,000 volumes of her works were issued in less than ten years.

Cusack has been described as "a temperamental extremist", "eccentric and rebellious", "passionate and difficult, constantly at odds with her ecclesiastical superiors", who was "an early and fervent believer in the apparition of the Virgin Mary at Knock".

[9] In 1880 she published the pamphlet The Apparition at Knock; with the depositions of the witness[es] examined by the Ecclesiastical Commission appointed by His Grace the Archbishop of Tuam and the conversion of a young Protestant lady by a vision of the Blessed Virgin.

[6] While there are many local shrines throughout Ireland, Margaret Anna Cusack joined Canon Ulick Bourke and Timothy Daniel Sullivan in promoting Knock as a national Marian pilgrimage site.

White, professor of history at Dayton University, the Knock pilgrimages and the Land League developed simultaneously along parallel lines.

[5] Cusack planned to establish a training school for young women intending to emigrate so that they would have some job skills when they reached America.

Cusack believed that the Poor Clare's had been brought to Kenmare instead of the Presentation Sisters for political reasons,[12] a claim biographer Philomena McCarthy disproved and attributed to a disturbed mind.

In 1884, during an audience with Pope Leo XIII to seek his support, Cusack obtained permission for a dispensation to leave the order of the Poor Clares and found a new congregation, the Sisters of St. Joseph of Peace, intended for the establishment and care of homes for friendless girls, where domestic service would be taught and moral habits inculcated.

Margaret Anna Cusack passed into obscurity for a long time, until as a result of Vatican II, religious orders were encouraged to review their roots and the intent of their founders.

...I believe the majority of Englishmen have not the faintest idea of the way in which the Irish tenant is oppressed, not by individuals, for there are many landlords in Ireland devoted to their tenantry, but by a system.

She issued Advice to Irish Girls in America (1872), which deals mainly with tips and suggestions relating to the profession of domestic service.

[24] Norman Vance sees Cusack as bridging the gap "...between eighteenth-century Catholic antiquarianism and the cultural nationalism of the Literary Revival."

She published more than fifty works, chief among which are A Student's History of Ireland; Lives of Daniel O'Connell, St. Patrick, St. Columba, and St. Bridget; The Pilgrim's Way to Heaven; Jesus and Jerusalem; and The Book of the Blessed Ones.