In 2015, crowd favourite and three-time Melbourne Cup runner-up Red Cadeaux had to be euthanised two-and-a-half weeks after the Cup as a result of complications from an injury suffered in that year's race.
The horse, which was based at County Tipperary in Ireland, had won more than $1.7million in prize money.
The Cliffsofmoher's death is the third time in five years a horse has died after running in the Melbourne Cup - an very bad record for the country's most prestigious turf event, and far in excess of the usual rate of fatalities in racing.
Regal Monarch, trained by Chris Waller, was euthanised after falling in race four past year, while British stayer Red Cadeaux was put down two weeks after falling and breaking a leg in the 2015 Melbourne Cup.More news: Facebook blocks more than 100 accounts, citing possible foreign influence
Racing Victoria confirmed jockey Ryan Moore was uninjured in the incident.
Just previous year Regal Monarch was also put down after breaking his leg at the carnival.
People for the Ethical Treatment of Animals (PETA) have called for an investigation into the horse's death - having previously demanded the race be scrapped altogether.
Cross Counter was the final victor of the Melbourne Cup after a nail-biting final, taking the lead in the very last seconds of the home stretch. Araldo was put down several hours after the race after he fractured his leg when he kicked a fence.More news: Kemp turns election system worries into a political weapon
"Our thoughts are with animal lovers across the country who have been affected by this loss, and confronted by the very real risks posed by racing to the horses involved", RSPCA Australia spokeswoman Jane Speechley said.
The Daily Telegraph has reported the star United Kingdom galloper had a fractured right shoulder and "could not be saved".
Seven commentator Bruce McAvaney described it as a "tragedy".
Number 2 horse Cliffsofmoher was injured within the first 600m of the Melbourne Cup. "He's really sweating up badly".More news: Champions League: Red Star Belgrade upset Liverpool
The 8-1 chance Cross Counter, who broke the track record when winning the Gordon Stakes at Glorious Goodwood in the summer, won by a length from the Hughie Morrison-trained Marmelo, with A Prince Of Arran third for Charlie Fellowes.