P&O Australia's $400 million luxury liner, which has capacity for almost 2000 passengers, is expected to arrive in Sydney on Monday morning.
The Explorer's return to full service will coincide with that of Ponant's Le Laperouse, which will begin operations between Darwin and Broome on April 28, joining local operators in time for the Kimberley cruise season.
NSW, Victoria and Queensland have outlined testing and vaccination requirements for passengers and crew in preparation for the ships to return.
However, Tasmania is still reviewing whether such a move is safe for the island state.
Peak body Cruise Lines International Association Australia says the lifting of the ban will be marked by "a carefully managed resumption of operations" in a sector that previously supported more than 18,000 jobs.
Cruise Lines' Australasian managing director Joel Katz says that before the pandemic more than a million Australians a year took an ocean cruise.
"We now have an opportunity to return to sailing and revive an industry that was worth more than $5 billion annually to the Australian economy," he said.
"While no setting is immune from COVID-19, the cruise industry's new protocols provide among the highest possible levels of prevention, detection and mitigation."
The move comes despite COVID-19 infections remaining high.
More than 32,000 new cases were reported across the nation on Sunday, along with 17 virus-related deaths, although seven of the eight announced by officials in Western Australia were historical.
The ACT did not report figures at the weekend.
There are currently more than 409,000 active COVID-19 cases in Australia. Some 3079 patients are in hospital care, and of these 137 have been admitted to ICUs and 30 require ventilation.
Meanwhile, Labor frontbencher Chris Bowen is isolating after testing positive.
"I was looking forward to a few days campaigning in regional Queensland and Brisbane but it isn't to be," he tweeted on Saturday.
Labor's Home Affairs spokeswoman Kristina Keneally and Home Affairs Minister Karen Andrews contracted the virus last week.
Elsewhere, Health Victoria is monitoring the new BA.4 or BA.5 Omicron variant after samples were confirmed in a catchment at Tullamarine, north of Melbourne.
The sub-variant has been recently detected in a small number of cases in South Africa, Botswana, Belgium, Denmark, the United Kingdom and Germany, but is not considered a cause for alarm.
LATEST 24-HOUR COVID-19 DATA FROM ACROSS AUSTRALIA:
NSW: 11,166 cases, four deaths, 1576 in hospital, 67 in ICU
Victoria: 7918 cases, one death, 431 in hospital, 30 in ICU
26°C