A man is in police custody after a grey Toyota mounted a curb and hit two pedestrians at Melbourne Showgrounds in Ascot Vale just before 5pm on Saturday.
It occurred on Langs Road, outside the Supanova Comic Con & Gaming Event, a two-day fan convention hosted at the showgrounds.
One pedestrian died at the scene while another was taken to hospital with life-threatening injuries, police said.
The injured pedestrian was a man aged in his 20s, Ambulance Victoria said.
He was treated at the scene for upper and lower body injuries and taken to the Royal Melbourne Hospital in a serious but stable condition, a spokesperson said.
Organisers offered their condolences hours after the incident but said the event would go ahead as planned on Sunday.
"We here at Supanova Comic Con & Gaming are deeply saddened and distressed by the incident that occurred outside the Melbourne Showgrounds this evening," they said in a statement on Saturday evening.
"Our thoughts and prayers go out to all those affected by the unspeakable tragedy that has happened on our doorstep".
The organisers declined to go into details as investigations were ongoing but said a silent tribute would be held before doors reopened.
"Supanova will continue to support all Supa-Fans that come through our doors tomorrow morning," they said.
"We will be holding a minute's silence in sympathy and solidarity of the affected families and friends at 10am before opening our doors to our event."
Officers arrested a man on Saturday evening to be interviewed by police.
He remains in custody, a Victoria Police spokesperson told AAP on Sunday morning.
Thousands of comic and gaming fans flock to Supanova every year, with the Melbourne event adding crowds of visitors to an already-busy area.
World-famous celebrities including Stranger Things cast member Jamie Campbell Bower and Andy Serkis, who played Gollum in Peter Jackson's Lord of the Rings movie trilogy, were set to headline the expo.