The officers suffered minor injuries as both protesters and homeless people were removed from the site by the public order response team at 1pm.
Acting Commander Stuart Bateson said 75 officers were required to remove those camped at the site due to safety concerns ahead of planned maintenance works at the historic railway station.
Protesters gathered at the site and joined in chants of “homelessness is not a crime”, “poverty is not illegal”, and “scum”.
One officer was allegedly punched in the back of the head by a female protester, Acting Commander Stuart Bateson said.
Police were filmed pushing the woman to the ground before detaining her, as the crowd shouted “let her go!”
Moments later, an elderly man drove a mobility scooter towards police.
Another man was handcuffed by police and led away after punching a 9NEWS camera, shattering the lens.
One homeless person will be charged with public drunkenness.
Three protesters were arrested for a range of offences including assaulting a police officer, throwing objects at officers, resisting police and another protester was arrested for public drunkenness.
Police formed a human wall outside the station to block the rough sleepers from supporters, onlookers and media about 1.30pm.
Police closed Flinders Street between Swanston and Elizabeth streets, but it has since re-opened.
One homeless man, identified only as Justin, told 9NEWS he had been waiting “four years” for accommodation.
“I’ve got two little kids, one is 11 and the other is eight, and we’re just waiting for public housing,” he said.
A large number of response police officers are waiting around the corner from the site. (9NEWS/Sean Davidson)
“The governments bring refugees here, pushing us down the list further and further.”
The Andrews Government said the group will be offered accommodation as part of a $10 million plan to get homeless people into transitional housing.
The Homeless Persons Union of Victoria confirmed 40 transitional houses had been announced, but it would “fail to cover the 70 people with their names down on the list at Flinders Street”.
Billy, who did not wish to have her last name used, told 9NEWS “nobody chooses this”.
Homeless people have frequented the city’s busiest station for years but numbers swelled and tents were erected last month.
The Lord Mayor announced last month he would enact a bylaw to move rough sleepers on – a decision that attracted condemnation from homeless groups and the Greens but was backed by the Premier and police.