Described as a "tragedy" by veteran Seven commentator Bruce McAvaney, the UK raider pulled up lame as the field passed the finishing post for the first time.
Veterinarians rushed on to the track as soon as the race was completed as a tarp was erected around the fallen stayer.
Horrible news. The Cliffsofmoher suffered a fractured right shoulder when injured in the Melbourne Cup, unfortunately could not be saved. Thoughts with connections. @Racing
After an eye-catching fourth at his Australian debut in the group one Caulfield Stakes and a third in the Caulfield Cup, the Lloyd Williams-owned stayer entered the Melbourne Cup a $17 chance.
But English jockey Ryan Moore had to pull up only 600m into the 3200m journey.
There have been several deaths in the past five years of the glamour race.
In 2014, Admire Rakti, who collapsed and died in his stall after the race, and Araldo, who broke his leg and was euthanased, were casualties.
The following year fan favourite Red Cadeaux shattered a leg and was put down on the track.