The Ruby Princess has commenced its departure from Port Kembla, south of Sydney, breaking its moorings on the start of a highly anticipated journey out of Australian waters.

Key points: The cruise ship has been linked to the coronavirus deaths of 21 Australians and two international passengers

The cruise ship has been linked to the coronavirus deaths of 21 Australians and two international passengers It first docked in Sydney Harbour on March 19, when almost 2,700 passengers disembarked

It first docked in Sydney Harbour on March 19, when almost 2,700 passengers disembarked A special commission of inquiry and a criminal investigation into the cruise are continuing

Since it first docked in Sydney Harbour five weeks ago, 21 Australians who were connected to the coronavirus-afflicted cruise ship have died.

As of this week, about one in every 10 cases of coronavirus in Australia could be linked to the Ruby Princess.

As it left the dock, a huge banner hanging off the stern of the ship read: "Thank you Illawarra", referring to the location where the cruise ship has been docked since April 6.

On Thursday, more than 350 crew members arrived at Sydney Airport after being allowed to disembark from the cruise ship.

About 25 buses, each with around 15 passengers to maintain social distancing, transported crew members to the airport for their flight to the Philippines.

NSW Police said 11 crew who tested positive for COVID-19 were taken to hotels to enter 14 days of quarantine.

The Ruby Princess on Thursday before it set sail. ( ABC News )

They said over three days, a total of 542 crew members were escorted from the ship to be repatriated to their home countries of Brazil, Canada, France, Germany, Mexico, New Zealand, the UK and US.

During that time, 33 crew were taken to Sydney hotels to be cared for in isolation until being cleared by NSW Health to fly back to their countries of origin.

The coronavirus-afflicted ship was given an order to leave by Australian Border Force officials. It was expected to leave on Sunday, but the departure was delayed to assess the health needs of the crew.

A special commission of inquiry and a criminal investigation into the cruise are continuing after almost 2,700 passengers were allowed to disembark in Sydney on March 19, despite more than a dozen people on board being tested for COVID-19.

The day before the ship docked there were about 300 cases in NSW, but the state had recorded a daily decrease in cases.

By March 20, there was a spike and the state's Health Minister told media he was "concerned" about the Ruby Princess as several passengers had already returned positive results.

NSW has now recorded eight Ruby Princess passenger deaths. Of the state's 2,976 coronavirus cases, almost 13 per cent are linked to the ship.

The cruise ship has been linked to the death of 21 Australians. ( ABC News )

Among approximately 900 international Ruby Princess passengers, the ABC has traced at least 35 coronavirus cases and two deaths.

When asked about who made the decision to let passengers off in Sydney, NSW Premier Gladys Berejiklian said, "all of us have to take responsibility".

But Australian Border Force Commissioner Michael Outram said NSW Health had given the green light for passengers to disembark.

Lawsuits are underway in the United States, and Australian firm Shine Lawyers is also investigating possible legal action on behalf of passengers.

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