Father Caspar Rehrl (1809 - 1881), an Austrian missionary, established a sisterhood of pioneer women under the patronage of St. Agnes of Rome to whom he had a special devotion.

[2] The arrival of Mary Hazotte in 1863 gave the fledgling community a new life and leadership when she, in 1864 at the age of 17, was elected general superior.

Women and men of any religious background who are single, married, or divorced and desire to live out the Congregation's mission without professing the three vows are known as Associates.

The Congregation sponsored Agnesian HealthCare in Fond du Lac, Wisconsin, until 2018, when it transferred sponsorship of its medical ministries to SSM Health.

In 2023, the congregation was recognized by Catholic Climate Covenant with a "U.S. Laudato Si' Champions Award" in the "Religious Order" category.