The Children’s Mission to Children was founded in 1849 by the generous impulse of Fannie S. Merrill, the nine-year-old daughter of a Unitarian Sunday School teacher, to help the neglected and homeless children of Boston. Fannie Merrill, believing that children could help other children, contributed the first pennies. Support then grew among the children of her Sunday School and among the children of other Sunday Schools.

The organization was incorporated in 1864 as the Children’s Mission to the Children of the Destitute in the City of Boston. In the early years, a missionary was hired to work among the children and their families but this soon proved inadequate. Money was then raised for a home on Tremont Street where abandoned children and ones whose families were unable to keep them were given shelter. The organization soon realized, however, that this type of institution was a poor substitute for a real home. Beginning in 1900, children were boarded in private homes and by 1907 the home on Tremont Street was finally abandoned in favor of foster home care. In 1913 the organization changed its name to the Children’s Mission to Children.

In 1914, Dr. Richard Cabot of the Massachusetts General Hospital brought out the importance of foster homes for hospitalized, convalescent children who were no longer acutely ill but were not well enough to return home without adequate medical supervision. Since rheumatic fever and chorea sufferers were particularly susceptible to unfavorable home conditions, a special type of convalescent home developed where doctors could be sure their orders of rest and care were carried out under the competent care of a foster mother, yet in the non-institutional atmosphere of a true home.

By 1934, ninety percent of the cases handled by the Children’s Mission were rheumatic fever victims. With improved medical treatments, this percentage dropped to twenty-four in 1952. The Children’s Mission became affiliated with the Children's Hospital Medical Center in 1949.

The name of the organization was once again changed in 1967 to the Parents’ and Children’s Services of the Children’s Mission. By this time the focus of the organization had also shifted from providing services to families with sick or handicapped children to working with troubled and emotionally disturbed children.