The Nursery and Child's Hospital was founded on May 2, 1854 by Mrs. Cornelius DuBois. The original name of the organization was The Nursery for the Children of the Poor Women. The Hospital started out as a nursery for wet nurses to leave their children while they worked. At the time, children of wet nurses were dying because of lack of food and care. The charity wanted to reduce the death rate among wet nurses' children. The location for the Nursery was the corner of 15th Street and 6th Avenue. Once the charity started, it became clear that a hospital was needed to take care of the children and their mothers. In 1857, the charity created a hospital for children located at 51st street and Lexington Avenue. The Hospital was the first hospital in the United States of America to treat children under the age of 12. On March 6, 1857, the charity changed it name to the Nursery and Child's Hospital. Over the years the Hospital would expand, offering more and more care to the children of the poor in New York City and the surrounding area.

The Hospital ran largely on donations and state funds. In 1858, wet nurses were charged $5 per child a month to leave their children at the Hospital. The children received boarding, food, an education and medical care from the Hospital. Patients of the Hospital were charged $6 a month. If a pregnant woman could not pay for staying at the Hospital she had to wet nurse another child beside her own for 3 months after birth. If the woman's own child died, she had to wet nurse 2 children. Women hired to be wet nurses at the Hospital were paid $5 a month and received food, medical care, and an education for her and her child. People could hire a wet nurse from the Hospital at a premium of $5. The Hospital charged so little for services that it was necessary to obtain funding from elsewhere. State and federal grants and donations were needed to cover operating cost. The Hospital's largest donation drive was its Annual Charity Ball that started in 1856 and would continue until it closed. The Annual Charity Ball would raise anywhere from five to fifteen thousand dollars a year.

From the beginning the Nursery and Child's Hospital had to deal with children being abandoned at the Hospital. Children were considered to be an orphan, if their parents did not pay for them for a week or they were left at the Hospital. Thus, a foundling home was needed at the Hospital. People could adopt children from the Hospital, but it was done between the parents and the adopting family or another charity and the adopting family. The Nursery and Child's Hospital would take care of children up to the age of 12. Children that were over the age of 12 were sent back to their parents or to other charities based on their parents' faith. Many of the children ended up at the Children's Aid Society and on the orphan trains.

The Nursery and Child's Hospital adhered to Christian standards. Church services occurred every Sunday with clergymen from different denominations leading the service, and there was, also, a bible study once a week. Originally, the founders of the Hospital only wanted to serve women who were married, but it soon became clear that the services were needed by unmarried women who were pregnant or "women who were in sin." Eventually, the Hospital allowed women who were unmarried and pregnant to stay at the Hospital. These women had to learn domestic skills and go to church while at the Hospital. Only the women who complied with all of Hospital's rules were considered "cleaned", no longer living in sin and fit to go back into society. The Hospital did its best to try to marry the unmarried women or employ them somewhere so that they could raise a family. Women who were pregnant for a second time that came to the Hospital were refused and sent to other charities or to families that churches had paid to take in pregnant women.

The Nursery and Child's Hospital had a lot of support from many different charities and societies in New York City. Some of the charities and societies working with the Nursery and Child's Hospitals were the Children's Aid Society, St. Thomas Helping Hand's Society, St. Thomas Church, Harlem's Relief, Holy Communion, All Soul's Employment Society, Hand in Hand, Women's Loyal League, Church Benevolent Society, Charity Organization Society, St. George's Employment Society, Brick Church Employment Society, Friend's Employment Society, Madison Avenue Reformed Church, Manhattan Trade School, Doe Ye Nexte Thynge Society, Christ Church Employment Society, and Tenten Sewing Class for the Nursery and Child's Hospital. The Nursery and Child's Hospital was, also, involved with the New York City community. During the Civil War the 51st street and Lexington Avenue branch of the Hospital served as a hospital for wounded soldiers. In 1902, the Hospital started to run a soup kitchen to feed the poor. In 1910, the Nursery and Child's Hospital took over the New York Infant Asylum located at Amsterdam Avenue and West 61st street.

In 1859, a servant's school started to operate at the Hospital. The goal of school was to teach children and unwed mothers important skills, so that they could work as a servant or a farmer. The servant school became very popular, and on May 1st 1869, the Country Home and Hospital in West New Brighton, Staten Island opened. The Country Home and Hospital would become known as the Country Branch of the Nursery and Child's Hospital. The Country Branch opened because it was believed that country air was the best thing to help people recovering from contagious diseases, and the school needed more room to operate. Children between the ages of 5-12 were sent to the Country Branch as a boarding school. There the children would be educated in reading, writing, arithmetic, farming, sewing, and other domestic skills. The vegetables produced by farming went to feed the country and city branches of the Hospital and the excess would be sold to make money for the Hospital. The sewing class would sew clothing and linens to be used in the Hospital. In 1893, a summer school was open at the Country Branch. The Nursery and Child's Hospital worked with Mount Sinai Hospital to develop a program to train nurses in obstetrics in 1895. On November 7th 1904, there was a fire at the Country Branch destroying the main building. In April 25th 1905, the Country Branch was closed because it no longer met the standards to operate by the Board of Health. The closure was thought to be temporary, until money could be raised to do the necessary upgrades at the Country Branch. It appears that the money was never raised to reopen and the need for the Country Branch disappeared because the public school system in the early 1900's had started to take over the function of the servant's school.

In 1930's, the Nursery and Child's Hospital had trouble operating and staying out of debt. In November 21, 1934, the New York Hospital expressed interest in taking over all of the Nursery and Child's Hospital, except for the foster home department, erasing all the debts of the Hospital. The Hospital agreed to accept the New York Hospital's proposal and the Nursery and Child's Hospital dissolved with its various departments taken over by other institutions within New York City. Its foster home department continued as the New York Child's Foster Home Service, which was started and funded by the Sullivan Fund.