Ignacia del Espíritu Santo began her work in 1684, after discerning her vocation in a retreat administered by her spiritual director, the Czech Jesuit priest Pablo Clain (also known as Paul Klein).

At the age of twenty-one she left home and launched an uncertain effort to found a group of religious sisters who worked outside cloister, which was quite rare in those days.

They ran a school for forty-five girls – Filipinas, Spaniards, and mestizas – imparting lessons in Christian living along with training in reading, sewing, and embroidery.

From 1748 to 1770 the beatas assisted the Jesuit Fathers in conducting spiritual retreats,[3] and extended their work to provinces in Luzon in groups of two or more as circumstances permitted, reanimating the faith of those who had fallen away from the sacraments.

While the Philippine Revolution of 1896 and the Spanish–American War caused deprivations for the Sisters in Mindanao, they were able to care for the wounded in hospitals, and when peace was restored, opened new schools in Luzon and in the Visayas.

On 21 June 1902, the apostolic administrator of the Archdiocese of Manila, Martin García Alocer, approved the congregation's petition to convene members from the different mission stations for the purpose of electing a mother general.

Almost two years later on 12 January 1948 (the 200th anniversary of the death of the foundress) Pope Pius XII issued the Decree of Definitive Pontifical Approbation of the Constitutions, placing the congregation directly under Rome.

Archbishop of Zamboanga Luís del Rosario, SJ then serving as Apostolic Visitator of the congregation, played a vital role in the process which led to the granting of the final decree.

The golden jubilee of the Religious of the Virgin Mary in the United States was celebrated in the Cathedral of the Blessed Sacrament in Sacramento, California, on 18 July 2009.

The Philippines jubilee celebration that year was held at Our Lady of the Assumption Chapel with Gabriel Villaruz Reyes, Bishop of Antipolo, presiding.

In 2007, Pope Benedict XVI declared the foundress, Ignacia del Espiritu Santo, a Venerable of the Catholic Church: The servant of God, Ignacia del Espiritu Santo, Foundress of the Congregation of the Religious of the Virgin Mary, is found to possess in heroic degree the theological virtues of faith, hope and charity toward God and neighbor, as well as the cardinal virtues of prudence, justice, temperance and fortitude.

[14] The beaterio was damaged during the World War II, which led for the congregation to move to another location[15] The Bagumbayan Light and Sound Museum now stands on the site.

In 1950, it was transferred to Quezon City in a compound of over five hectares which, besides the motherhouse, has the chapel of Our Lady of the Assumption blessed and inaugurated in 1950, St. Mary's novitiate, juniorate, and infirmary, and near the front gate the three-storey Betania Retreat House and Luzon Regional Residence.