The hospital was established as the Eye and Ear Infirmary in 1863, by Andrew Sexton Gray, an Irish medical practitioner who had emigrated to Victoria.

[1] In 1870, Gray's infirmary merged with Ophthalmic and Orthopaedic Institution operated by Aubrey Bowen and Ewin Jones, and in 1878 the hospital was granted valuable land by the Victorian government in what was called Tank Reserve in East Melbourne.

[3] In 1945 Elizabeth Johns returned from military service with a Royal Red Cross to take on the role of matron.

The Emergency Department operates 24 hours a day, and handles around 47,000 presentations a year of which approximately 80 per cent are ophthalmology (eye) cases.

There is a tunnel underneath Victoria Parade which links the Eye and Ear to St Vincent's Hospital.