Qantas said a "number of passengers travelling in the same group on QF28 (between) Santiago and Sydney became unwell with a gastro intestinal illness" on the 14-hour journey to Australia.
Media reports said between 20 and 30 passengers were vomiting as they disembarked in Sydney and were met by a fleet of ambulances.
"It is believed the illness was contracted before boarding the aircraft and symptoms became evident during the flight," Qantas said in a statement.
"The aircraft has been met by medical staff to look after the unwell passengers."
As a precaution, Qantas said all other passengers on the flight were advised to monitor their health closely over the next 24-48 hours.
Health authorities said they had been advised that "26 passengers returning on a Qantas flight from Santiago, Chile, developed vomiting and diarrhoea on the plane, consistent with norovirus infection, a common cause of outbreaks of gastroenteritis in Australia and elsewhere".
"New South Wales Health has provided Qantas with a letter and factsheet about viral gastro to distribute to all departing passengers, as well as advice for cleaning and cabin staff," the state's health office said in a statement.
It said the sick group was assessed by paramedics and escorted out of the airport "with minimal exposure to other passengers" after they were cleared to go home.
Stomach bug triggers mass vomiting on Qantas flight