Australia has some of the world’s toughest gun control laws, adopted after its worst mass murder, when a gunman killed 35 people at Port Arthur in the island state of Tasmania in 1996.
Three security guards and a man queueing to enter were taken to hospital with gunshot injuries, police said in a televised news conference in Melbourne.
"It would appear that shots have been discharged from a car in this area into a crowd standing outside the nightclub," homicide inspector Andrew Stamper said.
The victims suffered "horrific injuries" from a weapon fired in close proximity, he added.
One guard died in hospital, another man was in critical condition and two escaped life-threatening injuries. One guard was shot in the face, the Age newspaper said.
However, there was no suggestion yet that the attack was terror-related, a police spokeswoman said by telephone.
Bloodstained clothing and bullet casings littered the street outside the entrance to the second-storey Love Machine nightclub early on Sunday.
Police urged witnesses who saw any vehicle moving at speed around 3 a.m. to come forward, and mentioned a black Porsche SUV that was later found burnt-out in the north Melbourne suburb of Wollert.
No arrests have yet been made, and investigation continues.
A murder-suicide last year in Western Australia that killed seven members of a family was the country's worst mass shooting since the Port Arthur case.
Neighbouring New Zealand has adopted legislation to ban semi-automatic firearms and assault rifles after its worst peacetime shooting in March, which killed 50 worshippers in two mosques in the city of Christchurch.
