Aubrey Thomas Mussen was born in Lachine, Quebec, on 21 December 1873, the son of William Mussen and Georgiana Hurlbert. He graduated from the McGill Medical School in 1900. After graduation, he married Virginia Reiman Hack (1881-1957). The couple moved to London so that Mussen could pursue his studies in pathology. He worked at the National Hospital in 1905-1906 and 1908 with Victor Horsley and Robert Clarke, two British neurosurgeons known for pioneering a stereotactic instrument that clamps onto the head in order to provide Cartesian coordinates of the brain for use in surgery and dissection. In 1909, Mussen left for Munich to work at the Psychiatric Klinik in Munich before returning to London as a neuropathologist for London's Medical Research Committee. During the First World War, he served as major-in-charge of the neurological wards at Ste. Anne's Hospital in Montreal. After the war, he joined Johns Hopkins Hospital as a neurological research associate. From 1930 to 1933, he worked as a researcher at the Carnegie Institute in Washington D.C. Mussen retired from professional life in 1933 and died on 11 January 1975.

Mussen is known primarily for his invention of the first human stereotactic device, designed in 1918 after Horsley and Clarke's apparatus.