Lewis Albert Sayre was born on February 29, 1820 in Bottle Hill (now Madison), New Jersey. After graduating from Transylvania University in 1839 and considering entering the ministry, Sayre began to study medicine. He graduated from the College of Physicians and Surgeons (now part of Columbia University) in New York in 1842 and became an orthopedic surgeon. In 1859 he was appointed surgeon to the Bellevue Hospital and in 1861 was one of the principal founders of the Bellevue Hospital Medical College. Sayre served as professor of both orthopedic surgery and clinical surgery, and when the Bellevue Hospital Medical College merged with the University Medical College at NYU in 1898, Sayre was appointed emeritus professor of orthopedic and clinical surgery in the consolidated institution. In addition to his work as a professor and surgeon, Sayre worked to improve sanitary conditions in New York and to stop the spread of cholera from sailors on ships entering New York City.