Drill ship Joides Resolution will recover sediments and rocks lying deep beneath the sea bed in a bid to discover how the region has behaved over the past tens of millions of years.
The recovered cores will be studied onboard, allowing scientists to address issues such as oceanographic history, extreme climates, sub-seafloor life, plate tectonics and earthquake-generating zones.
Co-chief scientist Jerry Dickens, from Rice University in Texas, said the region was a vital area to study changes in global climate.
"As Australia moved north and the Tasman Sea developed, global circulation patterns changed and water depths over Zealandia fluctuated," he said.
"This region was important in influencing global changes."
Australian National University's Neville Exon said the two-month expedition, setting out Friday from Townsville, would also help better understand major changes in the global tectonic configuration that started about 53 million years ago.
This is around the time that the Pacific "Ring of Fire", a hotspot for volcanoes and earthquakes, came into existence.
In the February scientific paper, lead author Nick Mortimer said experts had been gathering data to make the case for Zealandia being a continent for more than 20 years.
But their efforts had been frustrated because most of it was hidden beneath the waves.
"If we could pull the plug on the oceans, it would be clear to everybody that we have mountain chains and a big, high-standing continent," he said at the time.