In 1869, Bishop Michael Domenec, C.M., of Pittsburgh appealed to the Cincinnati community of Sisters of Charity for sisters to serve the needs of the growing Catholic population in his diocese. Sister Aloysia Lowe, three other Sisters of Charity, and two novices, left Cincinnati and arrived in Altoona, Pennsylvania, on August 20, 1870.
Sister Aloysia Lowe was named Mother Superior and Sister Anne Regina Ennis Assistant and Mistress of Novices. In quick succession, schools were opened in Blairsville, Johnstown, and the Pittsburgh neighborhoods of East Liberty, Sharpsburg, Lawrenceville, and South Side.

Roselia Foundling and Maternity Asylum was established in 1891. The Charity Hospital of Pittsburgh (later renamed Pittsburgh Hospital) was founded in 1897. The Pittsburgh Hospital School of Nursing opened in 1905 and the first class of five Sisters of Charity and five young women graduated in 1908. DePaul Institute for the Deaf (now DePaul School for Hearing and Speech) opened in 1908 at the invitation of Bishop Canevin. Providence Hospital opened in 1909, its School of Nursing in 1912.

Seton Junior College began in 1914. In 1918, the Commonwealth of Pennsylvania granted a charter establishing Seton Hill College (now Seton Hill University), a four-year liberal arts college for women.
The Sisters of Charity became a Pontifical Congregation in 1948 and made perpetual vows for the first time the following year. The Constitutions of the Sisters of Charity of Seton Hill were given definitive approval in 1957.

In 1960, four sisters were sent to Mokpo, South Korea, at the invitation of Bishop Harold Henry, SSC. The sisters serve in 11 of 14 dioceses in South Korea, ministering in education, social work, retreat work, and with the physically disabled.

Ministry continues to expand in new directions as the sisters move into parish ministry and social service, prison ministry, and a multitude of individual ministries. There are now 381 Sisters of Charity serving in schools, hospitals, parishes, social service agencies, and other apostolates in the United States, South Korea, Israel, and Ecuador.

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