Cushing was born in Cleveland, Ohio, the son of Bessie Williams; and Kirke Cushing, a physician whose family came to Hingham, Massachusetts, as Puritans in the 17th century. Harvey Cushing was the youngest of ten children. He graduated with an A.B. degree in 1891 from Yale University, where he was a member of Scroll and Key and Delta Kappa Epsilon (Phi chapter). He studied medicine at Harvard Medical School and was given his M.D. degree in 1895. Cushing completed his internship at Massachusetts General Hospital and then did a residency in surgery under the guidance of a famous surgeon, William Stewart Halsted, at the Johns Hopkins Hospital, in Baltimore. During his medical career he was a surgeon at Johns Hopkins Hospital, at the Peter Bent Brigham Hospital in Boston.

He married Katharine Stone Crowell on June 10, 1902. They had five children: William Harvey Cushing; Mary Benedict Cushing who married Vincent Astor and after a divorce married painter James Whitney Fosburgh; Betsey Cushing, who married James Roosevelt and later John Hay Whitney; Henry Kirke Cushing; and Barbara Cushing, the socialite wife of Stanley Grafton Mortimer and later William S. Paley.

He became a professor of surgery at the Harvard Medical School starting in 1912. He served in the U.S. Army Medical Corps as a surgeon with the American Expeditionary Forces in Europe during World War I, attaining the rank of Colonel. In that capacity, he treated Lt. Edward Revere Osler, the son of Sir William Osler, who was fatally wounded during the third battle of Ypres. From 1933 to 1937, when he retired, he worked at Yale University School of Medicine.

Cushing died on October 7, 1939 in New Haven, Connecticut, from complications of a myocardial infarction. He was interred at Lake View Cemetery in Cleveland. Interestingly, an autopsy performed on Cushing revealed that his brain harbored a colloid cyst of the third ventricle.

In the beginning of the 20th century he developed many of the basic surgical techniques for operating on the brain. This established him as one of the foremost leaders and experts in the field. Under his influence neurosurgery became a new and autonomous surgical discipline.

• He considerably improved the survival of patients after difficult brain operations for intracranial tumors.
• He used x-rays to diagnose brain tumors.
• He used electrical stimuli for study of the human sensory cortex.
• He played a pivotal role in development of the Bovie electrocautery tool with W.T. Bovie, a physicist.
• He was the world's leading teacher of neurosurgeons in the first decades of the 20th century.

Arguably, Cushing's greatest contribution came with his introduction to North America of blood pressure measurement. On visiting colleague Scipione Riva-Rocci, an Italian physician, Cushing was astonished at Riva-Rocci's non invasive way to measure intra-arterial pressure. In 1896, Riva-Rocci developed a wall-mounted mercury manometer linked to a balloon-inflated cuff that would measure the pressure needed to compress arterial systolic pressure, i.e. systolic blood pressure measurement. Riva-Rocci's design was based on a more primitive version developed by French physician Pierre Potain. Cushing brought back a sample of Riva-Rocci's sphygmomanometer, and blood pressure measurement became a vital sign and its use spread like wildfire across the US and western world as a direct contribution by Harvey Cushing. Its use remained until Russian physician Nikolai Korotkov included diastolic blood pressure measurement in 1920 (after he discovered the famed "Korotkoff sounds") with his modern sphygmomanometer, which also replaced the mercury manometer with a smaller, round dial manometer.

Cushing's name is commonly associated with his most famous discovery - Cushing's disease. In 1912 he reported in a study an endocrinological syndrome caused by a malfunction of the pituitary gland which he termed "polyglandular syndrome". He published his findings in 1932, as "The Basophil Adenomas of the Pituitary Body and Their Clinical Manifestations pituitary Basophilism".

Cushing was also awarded the 1926 Pulitzer Prize for Biography or Autobiography for a book recounting the life of one of the fathers of modern medicine, Sir William Osler. In 1930, Cushing was awarded the Lister Medal for his contributions to surgical science. As part of the award, he delivered the Lister Memorial Lecture at the Royal College of Surgeons of England in July 1930. Cushing was elected to the Royal Swedish Academy of Sciences in 1934.

In 1988, the United States Postal Service issued a 45 cent postage stamp in his honor, as part of the Great Americans series.

The Harvey Cushing/John Hay Whitney Medical Library at Yale University contains extensive collections in the field of medicine and the history of medicine. In 2005, the library released portions of its collection online, including the Peter Parker Collection which consists of a collection of portrait engravings and 83 mid-19th century oil paintings rendered by artist Lam Qua of Chinese tumor patients, and a biography of Harvey Cushing by John F. Fulton.