Mother Margaret Farrell George founded the Sisters of Charity of Cincinnati, in 1852, separating the community from the Sisters in Emmitsburg MD. The Sisters of Charity of Cincinnati: were founded on the model of Elizabeth Ann Seton, who founded the first community of religious women, native to the United States.
Catholics were few and far between in Cincinnati and throughout Ohio in the early decades of the nineteenth century. Most were poor Germans, but their number also included many of Swiss and Irish descent. The area around Cincinnati was initially part of the diocese of Bardstown, Kentucky. On 19 June 1821 the diocese of Cincinnati was created with Edward D. Fenwick appointed the first bishop.
In 1829, four Sisters of Charity from Emmitsburg, Maryland traveled 15 days by stage coach to Cincinnati, Ohio at the request of Bishop Fenwick. At that time the Diocese of Cincinnati encompassed the Northwest Territory of the United States (ultimately, the states of Illinois, Indiana, Michigan, Ohio and Wisconsin). The sisters opened St. Peter’s Girl’s Orphan Asylum and School.
Cincinnati experienced serious cholera epidemics in 1832-33 and in the summer of 1849. In the summer of 1833 alone, Cincinnati averaged forty deaths per day, with the immigrant population most heavily affected. Estimates are that 4 percent of the city's population died during this epidemic. The Sisters responded by providing health care and by caring for the suddenly increased numbers of orphans. In addition to the school and orphanage, they were involved in the “Mary and Martha Society” to visit the sick.
After superiors at Emmitsburg decided in 1850 to establish formal affiliation with the Daughters of Charity based in France, seven Sisters in Cincinnati, including Superior Margaret Cecilia Farrell George voted to decline affiliation on the basis that their foundress, Elizabeth Seton, intended that the community she founded be based in America. Sister Margaret George had entered the community at Emmitsburg early in 1812, and had filled the office of treasurer and secretary of the community, teaching in the academy during most of Mother Seton's life. The Sisters of Charity of Cincinnati became an independent diocesan order. Soon after foundation of the diocesan community, the Sisters opened St. Vincent's Asylum for Boys. In 1854 the Sisters founded Mount St. Vincent's Academy, Cedar Grove, in Price Hill, which later became Seton High School. A mission in Dayton, Ohio was established in 1857. In 1920 the Sisters founded the College of Mount St. Joseph in Delhi, the first Catholic college for women in Hamilton County, Ohio.