Too many empty seats and increasing competition from Mainland Chinese Carriers Contributed to the poor results, the Airline said.
The net loss of HK$575m ($74m; £60.1m) for 2016, was down from a HK$6bn profit the previous year.
It is only the third time the company has posted a full-year loss since it was founded in 1946.
The airline's shares fell by 7% in early trading, but then recovered.
Cathay Pacific is facing fierce rivalry from mainland Chinese and Middle Eastern airlines that are expanding rapidly in the region.
Carriers such as Air China and China Eastern are offering more direct services from the mainland, making it less attractive for passengers to travel via Hong Kong.
The airline said "intense competition" from those rival carriers contributed to sales dropping by 9.4%.
Demand for lucrative business and first class seats had also gone down, said chairman John Slosar.
Passenger yield - the average fare paid per mile per customer - is a closely watched indicator of an airline's financial health.
For Cathay Pacific that figure fell by 9.2% in 2016, while yield on cargo services fell by 16.3%.
Mr Slosar warned that 2017 would be similarly "challenging".
In January, the airline announced a major restructuring programme which would see jobs axed, although it remains unclear how many roles will be affected.
"Our organisation will become leaner," the carrier said in a statement to the Hong Kong exchange on Wednesday.