Sacks began consulting at chronic care facility Beth Abraham Hospital (now Beth Abraham Health Service) in 1966. At Beth Abraham, Sacks worked with a group of survivors of the 1920s sleeping sickness, encephalitis lethargica, who had been unable to move on their own for decades. These patients and his treatment of them were the basis of Sacks' book Awakenings.
His work at Beth Abraham helped provide the foundation on which the Institute for Music and Neurologic Function (IMNF) is built; Sacks is currently an honorary medical advisor. In 2000, IMNF honored Sacks, its founder, with its first Music Has Power Award. The IMNF again bestowed a Music Has Power Award on Sacks in 2006 to commemorate "his 40 years at Beth Abraham and honor his outstanding contributions in support of music therapy and the effect of music on the human brain and mind".
Sacks was formerly employed as a clinical professor of neurology at the Albert Einstein College of Medicine and at the New York University School of Medicine, serving the latter school for 42 years. On , Columbia University College of Physicians and Surgeons appointed Sacks to a position as professor of clinical neurology and clinical psychiatry, at the same time opening to him a new position as "artist", which the university hoped will help interconnect disciplines such as medicine, law, and economics. Sacks remains a consultant neurologist to the Little Sisters of the Poor, and maintains a practice in New York City.
Sacks describes his cases with little clinical detail, concentrating on the experiences of the patient (in the case of his A Leg to Stand On, the patient was himself). The patients he describes are often able to adapt to their situation in different ways despite the fact that their neurological conditions are usually considered incurable. His most famous book, Awakenings, upon which the movie of the same name is based, describes his experiences using the new drug L-Dopa on Beth Abraham post-encephalitic patients. Awakenings was also the subject of the first film made in the British television series Discovery.
In his other books, he describes cases of Tourette syndrome and various effects of Parkinson's disease. The title article of The Man Who Mistook His Wife for a Hat is about a man with visual agnosia and was the subject of a 1986 opera by Michael Nyman. The title article of An Anthropologist on Mars is about Temple Grandin, a professor with high-functioning autism.
In his book The Island of the Colorblind Sacks describes the Chamorro people of Guam, who have a high incidence of a form of Amyotrophic lateral sclerosis (ALS) known as Lytico-bodig (a devastating combination of ALS, dementia, and parkinsonism). Along with Paul Cox, Sacks is responsible for the resurgence in interest in the Guam ALS cluster, and has published papers setting out an environmental cause for the cluster, namely toxins such as beta-methylamino L-alanine (BMAA) from the cycad nut accumulating by biomagnification in the flying fox bat.
Sacks's writings have been translated into 21 languages, including Catalan, Finnish, and Turkish. In addition to his books, Sacks is a regular contributor to The New Yorker and The New York Review of Books, as well as other medical, scientific, and general publications. He was awarded the Lewis Thomas Prize for Writing about Science in 2001. Oxford University awarded him an honorary Doctor of Civil Law degree in June 2005. In March 2006, he was one of 263 doctors who published an open letter in The Lancet criticizing American military doctors who administered or oversaw the force-feeding of Guantanamo detainees who had committed themselves to hunger strikes.
Sacks's work has been featured in a "broader range of media than those of any other contemporary medical author and in 1990, The New York Times said he "has become a kind of poet laureate of contemporary medicine".
At the same time, Sacks has faced criticism in the medical and disability studies communities. His account of abilities of autistic savants has been questioned, and Arthur K. Shapiro—described as "the father of modern tic disorder research—referring to Sacks celebrity status and that his literary publications received greater publicity than Shapiro's medical publications, said he is "a much better writer than he is a clinician". Howard Kushner's A Cursing Brain? : The Histories of Tourette Syndrome, says Shapiro "contrasted his own careful clinical work with Sacks's idiosyncratic and anecdotal approach to a clinical investigation". More sustained has been the critique of his political and ethical positions. Although many characterize Sacks as a "compassionate" writer and doctor, others feel he exploits his subjects. Sacks was called "the man who mistook his patients for a literary career" by British academic and disability-rights activist Tom Shakespeare, and one critic called his work "a high-brow freak show". Such criticism was echoed in the movie The Royal Tenenbaums, with Bill Murray's comic portrayal of "an Oliver Sacks-like neurologist who snickers openly at his weirdo subjects". Sacks himself has stated "I would hope that a reading of what I write shows respect and appreciation, not any wish to expose or exhibit for the thrill," he sighs, "but it's a delicate business."
Sacks has been awarded honorary doctorates from the College of Staten Island (1991), Tufts University (1991), New York Medical College (1991), Georgetown University (1992), Medical College of Pennsylvania (1992), Bard College (1992), Queen's University (Ontario) (2001), Gallaudet University (2005), University of Oxford (2005), Pontificia Universidad Católica del Perú (2006). He was made an honorary member of the honors society of Saint John's University on October 5, 2008.
Sacks was appointed Commander of the Order of the British Empire (CBE) in the 2008 Birthday Honours.
Asteroid 84928 Oliversacks, discovered in 2003 and in diameter, was named in his honor.