The grey Toyota struck two people at Melbourne Showgrounds just before 5pm on Saturday as the Supanova Comic Con and Gaming expo began wrapping up its first day.
"Sadly, one of the pedestrians, who is yet to be formally identified, died at the scene," police said in a statement.
The other pedestrian was taken to hospital with life-threatening injuries after the vehicle mounted the kerb at Langs Road in Ascot Vale, police said.
Investigations are ongoing but officers have arrested a man, who is set to be interviewed.
Victoria Police are calling on anyone who witnessed the incident, with CCTV/dashcam vision or information to contact Crime Stoppers.
Thousands of comic and gaming fans flock to Supanova Comic Con and Gaming 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 trilogy, are headlining the expo.
The program features an indie games showcase, panels on comic creation and Q&As with some of the stars.
Saturday's events were scheduled to conclude about 5.30pm.
Supanova Comic Con and Gaming also holds annual expos in Sydney, Brisbane, Perth, Adelaide and the Gold Coast.
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