Two other people are in hospital after being stabbed in a busy Bourke Street on Friday afternoon.
The footage, uploaded to Twitter, also shows pedestrians alternately hovering nearby and trying to make a quick exit from the scene.
Victoria Police said the unnamed attacker is in "critical condition" at the hospital following the incident, which left one of the victims dead.
Paramedics said they assessed three people at the scene, one with a neck injury: "They are in a suspected critical condition".
Two other victims have been taken to hospital with injuries. Their condition is not yet know.
Witnesses said they heard a loud explosion and saw a auto bust into flames outside Target on Bourke Street, between Swanston and Russell Streets, about 4.20pm.
The suspect is then shot by police and falls to the ground.
"We will keep an open mind as to whether there is any link, it's very early stages in the investigation", he said.
Police are urging any witnesses to attend Melbourne West police station to provide a statement, while anyone with vision or photographs from the incident is being urged to upload footage to the Victoria Police Facebook site.More news: North Korea 'really angry' at USA as tensions rise
'The exact circumstances are yet to be determined at this stage.
The chaos started when 3AW was flooded with calls from people at the scene who had witnessed a vehicle "bursting into flames" just after 4pm on Friday. Meanwhile, a auto can be seen blazing on the side of the pavement at the scene.
It was too early to say if the incident was terror-related, they said.
Another said they heard "what sounded like a bomb and gun shot". Victoria Police said at a press conference.
The incident comes as a trial continues into the horrifying rampage in Bourke St in January a year ago.
'Police response was swift and overwhelming.
Another witness said: "Big fire". I heard at least one gunshot initially, ' one said.
James Gargasoulas is accused of deliberately driving his vehicle into pedestrians on Bourke Street, hitting 33 people.