After going through the medical course at the London Hospital and becoming a member to the Royal College of Surgeons in 1858, he studied abroad in Paris, Vienna and Budapest where he learned the use of the newly-invented laryngoscope under Johann Czermak.
Returning to London in 1862, he worked at the London Hospital and earned his degree in medicine. In 1863 he won the Jacksonian prize at the Royal College of Surgeons for an essay on the Pathology and Treatment of Diseases of the Larynx: The Diagnostic Indications to include the Appearance as Seen in the Living Person. He was the first to use the terms abductors and adductors to describe the muscles that govern the opening and closing of the glottis. He then devoted himself to becoming a specialist in diseases of the throat.
In 1863 the Throat Hospital in King Street, Golden Square, was founded, largely owing to his initiative, and by his work there and at the London Hospital (where he was one of the physicians from 1866 to 1873) Morell Mackenzie rapidly became recognized throughout Europe as a leading authority, and acquired an extensive practice.
His reputation grew even more with the publication of three important books, which became the founding stones of the new specialty of laryngology:
In 1887 Mackenzie was one of the founders of the Journal of Laryngology and Rhinology and of the British Rhino-Laryngological Association.
So great was his reputation that in May 1887, when the crown prince of Germany (afterwards the Emperor Frederick III) was attacked by the affection of the throat of which he ultimately died, Morell Mackenzie was specially summoned to attend him. The German physicians who had attended the prince since the beginning of March (Karl Gerhardt, and subsequently Adalbert Tobold, Ernst von Bergmann, and others), had diagnosed his ailment on May 18th as cancer of the throat; but Morell Mackenzie insisted (basing his opinion on a microscopical examination by the great pathologist Rudolph Virchow of a portion of the tissue) that the disease was not demonstrably cancerous, that an operation for the extirpation of the larynx (planned for the May 21st) was unjustifiable, and that the growth might well be a benign one and therefore curable by other treatment. The question was one not only of personal but of political importance, since it was doubted whether any one suffering from an incapacitating disease like cancer could, according to the family law of the Hohenzollerns, occupy the German throne; and there was talk of a renunciation of the succession by the crown prince. It was freely hinted, moreover, that some of the doctors themselves were influenced by political considerations. At any rate, Morell Mackenzie's opinion was followed: the crown prince went to England, under his treatment, and was present at the Jubilee celebrations in June. Morell Mackenzie was knighted in September 1887 for his services, and decorated with the Grand Cross of the Hohenzollern Order. In November, however, the German doctors were again called into consultation, and it was ultimately admitted that the disease really was cancer; though Mackenzie, with very questionable judgment, more than hinted that it had become malignant since his first examination, in consequence of the irritating effect of the treatment by the German doctors. The crown prince became emperor on March 9th 1888, and died on June 15th. During all this period a violent quarrel raged between Sir Morell Mackenzie and the German medical world. The German doctors published an account of the illness, to which Mackenzie replied by a work entitled The Fatal Illness of Frederick the Noble (1888), the publication of which caused him to be censured by the Royal College of Surgeons.
After this sensational episode in his career, the remainder of Sir Morell Mackenzie's life was uneventful, and he died somewhat suddenly in London, on February 3, 1892 and was buried in the churchyard at Wargrave in Berkshire where he had a house in the country. He published several books on laryngoscopy and diseases of the throat.
Biographies of Mackenzie were published by H.R. Haweis (1893) and R. Scott Stevenson (1946).