Zealous fell on the third fence before the finish.
Jockey Aaron Lynch was unconscious for a short time, reports said.
Jumps racing in Victoria and South Australia remains under scrutiny, with animal welfare advocates suggesting it is cruel and the deaths of racehorses unacceptable.
Six of the 12 horses finished the race.
The Victoria RSPCA said two horses fell and another two were brought down during the race.
"Tragically, Zealous did not survive this incident," it said.
"Jumps racing must end so horses are not forced to endure unnecessary suffering."
The five other horses who did not complete the course were Morsonique, Gravitas, Last Shogun, Nuvolari and Guara Grove Beast.
There were no other injuries to horses or jockeys.