The man who allegedly ran over a group of pedestrians, killing one and injuring five others, was found standing on top of his car "ranting and uttering" before he was arrested, Victoria Police have said.

The 26-year-old driver of a white Toyota sedan turned left onto Bourke Street from Elizabeth Street and veered onto the right-hand side of the road, hitting a group of pedestrians, before accelerating and crashing into a Hyundai and a Mazda.

Investigators are still trying to determine if the incident was deliberate or reckless, Police Chief Commissioner Shane Patton said.

"He did make some comments which will be important for what that means for the investigation, and whether there was intention or not behind the incident," Patton said.

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Three pedestrians, a 26-year-old man from Yarra South, a 23-year-old woman from China and a 35-year-old woman from Docklands, were struck by the Toyota at a tram stop on Swanston Street.

The 26-year-old man is suffering a suspected broken pelvis and head injuries. The 35-year-old woman has a broken arm and head injuries, while the 23-year-old woman is suffering from a neck fracture, broken pelvis and head injuries.

All three are in a serious but stable condition.

The 76-year-old driver of the Hyundai was killed whilst two people in the Mazda, which is believed to have been an Uber, were taken to hospital.

Two police officers who were nearby arrested the Toyota driver, who was standing on the roof of the car "ranting," Patton said.

He also confirmed that the incident has no terror links.

The driver has been deemed unfit for police interview following a mental health assessment and remains under police guard at the Royal Melbourne Hospital.

Premier Dan Andrews also offered his condolences and thanked the members of the public who rushed to assist those injured.

"I wanted to send out our deepest sympathies to the family of the 76-year-old man who has died in this incident," Andrews said while addressing the media.

"Can I [also] thank those many many Victorians who were on the scene who offered their hand or love or support." 

Melbourne resident Joey Tam witnessed the collision as she was leaving her workplace on Bourke Street.

"I heard a lot of people screaming, […] I saw a body fly up and hit the ground," she told Weekend Today hosts Jayne Azzopardi and Clint Stanaway.

"I felt really helpless at the time because this has happened again, and you can't stop someone doing something silly on the streets."

"I feel unsafe as someone who works on Boukre Street, I cross that road every day." 

Tam also witnessed the 2017 attack on Bourke Street Mall, which killed six and left 37 others injured when now-convicted murderer James Gargasoulas ran over dozens of pedestrians.

Areas between Bourke Street, Swanston Street and Exhibition Street remain closed.

Earlier, Ambulance Victoria said there had been five people injured; one was taken to the Royal Melbourne Hospital in a serious condition, two to the Alfred in a stable condition, and one to St Vincent's in a stable condition.