[8] The Jews' Hospital in the City of New York, as it was called until adopting its current name in 1866,[9] was built on West 28th Street in Manhattan, between Seventh and Eighth Avenues, on land donated by Simson.

[10][11] The Jews' Hospital felt the effects of the escalating Civil War in other ways, as staff doctors and board members were called into service.

Dr. Israel Moses served four years as lieutenant colonel in the 72nd New York Infantry Regiment;[12] Joseph Seligman had to resign as a member of the board of directors, as he was increasingly called upon by President Lincoln for advice on the country's growing financial crisis.

[15][16] Now called Mount Sinai Hospital, the institution forged relationships with many physicians who made contributions to medicine, including Henry N. Heineman, Frederick S. Mandelbaum, Bernard Sachs, Charles A. Elsberg, Emanuel Libman, and, most significantly, Abraham Jacobi, known as the father of American pediatrics and a champion of construction at the hospital's new site on Manhattan's Upper East Side in 1904.

Its faculty has made significant contributions to gene therapy, cardiology, immunotherapy, organ transplants, cancer treatments, and minimally invasive surgery.

Among the innovations at Mount Sinai were performing the first blood transplant into the vein of a fetus in 1986, and the development of a technique for inserting radioactive seeds into the prostate to treat cancer in 1995.

[21] Dr. Jack M. Gorman, formerly Department Chairman of Psychiatry at Mount Sinai, engaged in a long-term inappropriate sexual relationship with a patient prior to October 2005.

[22] In January 2013 David L. Reich was the first openly gay medical doctor named interim president of Mount Sinai Hospital as reported by The New York Times.

[24][25] In August 2016 Dennis S. Charney, the dean of the medical school, was shot and wounded as he left a deli in his home town of Chappaqua, New York.

[30][31] Three doctors were convicted of violating anti-kickback laws by accepting bribes disguised as speaker fees to write prescriptions to a highly addictive fentanyl opioid painkiller.

[32][33][34] Alexandru Burducea, a pain management doctor and anesthesiologist who previously worked at Mount Sinai, was sentenced in January 2020 to 57 months in prison.

[5][6] As of 2019[update], the entire Mount Sinai Health System had over 7,400 physicians, 2,000 residents and clinical fellows, and 42,000 employees, as well as 3,815 beds and 152 operating rooms, and delivered over 16,000 babies a year.

The system encompasses the Icahn School of Medicine at Mount Sinai and seven hospital campuses in the New York metropolitan area, as well as a large, regional ambulatory footprint.