The Children's Hospital of Buffalo was established on May 23, 1892 by thirteen women with a staff of eight, a head nurse, five nurses-in-training, a housekeeper and a cook. Three male physicians were available, but they had permanent appointments at Buffalo General Hospital.

By 1907 the Children's Hospital had a woman superintendent and one of the first woman physicians in Buffalo on staff. The Board of Managers was run by women through the 1960's and into the 1970's when men first served on the board. Beginning prior to World War I the Children's hospital was committed to care for children of all races, ethnicities and backgrounds.

From inception, a goal of the hospital was to have free beds for children of limited means. The Children's Hospital has always been beloved and well supported by the Buffalo community. From these humble beginnings and with the commitment of the community the Children's Hospital has grown in stature so that currently it is ranked 17th among 125 University based Pediatric Departments, 200 accredited pediatric training programs and 1000 Pediatric departments.

The Children's Hospital of Buffalo is ranked 6th in the Northeast, ahead of Yale, Massachusetts General Hospital and Duke. The Children's Hospital is designated a center of Excellence by the State University of New York.

The Digestive Diseases and Nutrition Center (DDNC), formerly the Division of Pediatric Gastroenterology and Nutrition, was established at the Children's Hospital of Buffalo in 1976, as one of the first centers for the treatment of children with gastrointestinal and nutrition problems in the United States by Dr. Emanuel Lebenthal. The International Institute for the study of diarrheal diseases, funded through USAID, was housed within the DDNC from 1985 through 1989 and made major contributions to the treatment of diarrheal diseases in the world.

Recently the DDNC has undergone expansion with an increased availability of off site clinics, a clinical and basic science research program and expanded laboratory assays.