Chief executive Rupert Hogg, who has held the top job since 2017, has been replaced with immediate effect, the Hong Kong-based airline confirmed.
Chief customer and commercial officer Paul Loo has also stepped down.
Augustus Tang has been appointed to succeed Mr Hogg. Ronald Lam, currently chief executive of subsidiary Hong Kong Express, has been appointed to replace Paul Loo.
Mr Hogg said in a statement that “these have been challenging weeks for the airline” and that it was “right” that he and Mr Loo took “responsibility as leaders of the company”.
Cathay Pacific has found itself swept up in controversy over the Hong Kong protests, which have rocked the city over the past 10 weeks.
Earlier this week the airline cancelled all its flights in and out of Hong Kong International Airport, a major Asian hub, as protestors occupied the main terminal to denounce police brutality.
The airline said it would comply with a directive from the Civil Aviation Administration of China (CAAC), which ban any employees who took part in the protests from working on mainland China-bound flights.
The carrier also sacked two pilots and two airport employees for their involvement in the protests.
Chairman John Slosar said: “Augustus Tang and Ronald Lam have the experience and depth of knowledge of aviation and our people to be strong and effective leaders of Cathay Pacific at this sensitive time.
“Hong Kong is a fantastic home for our airline. It is a world-class city and has a premium airport which is the biggest international passenger and cargo hub in Asia.
“Cathay Pacific is fully committed to Hong Kong under the principle of ‘One Country Two Systems’ as enshrined in the Basic Law. We are confident that Hong Kong will have a great future.”