About two dozen asylum seekers have left Manus Island detention centre as part of Australia's resettlement deal struck with the United States.
The Refugee Action Coalition said about 22 refugees, including Sudanese, Afghan, Rohingya and Iranian asylum seekers, were taken to Port Moresby on Sunday.
The group, along with three others already in Port Moresby, will be flown to the US on Wednesday.
Refugee Action Coalition spokesman Ian Rintoul said it was a bittersweet moment for the refugees.
"They're unhappy that they have lost four years of their life," he told AAP on Sunday.
"But are very happy at the possibilities of having a safe life and rebuilding."
The move was flagged on Wednesday by Prime Minister Malcolm Turnbull, who said it was a sign of the strong relationship Australia shared with America.
The agreement was struck with the Obama administration and caused tensions to flare between Mr Turnbull and US President Donald Trump, who called the deal "dumb" before agreeing to honour it.
Up to 1250 refugees in Papua New Guinea and Nauru will be taken to America in return for Australia accepting asylum seekers from Central America.
More than 1600 refugees have expressed interest in US resettlement.
Mr Rintoul said the departure of the 25 people raised big questions about the future of those who remain.
"Things that have been said to the initial group of people make it seem very likely that there is going to be some months, perhaps, before there's another group who are going to go from Manus Island," he said.
Australia allocated $55 million to a Cambodia resettlement deal which was only taken up by up to seven people and is largely seen as a failure.
The majority instead chose to return to their country of origin.
