Around 1,100 workers at P&O Ferries are to be made redundant as part of a plan to make the business "viable and sustainable", the company said.
The plans involves more than a quarter of the workforce losing their jobs.
A spokesman for Dover-based P&O Ferries said: "Since the beginning of the crisis, P&O Ferries has been working with its stakeholders to address the impact of the loss of the passenger business.
"It is now clear that right-sizing the business is necessary to create a viable and sustainable P&O Ferries to get through Covid-19.
"Regrettably, therefore, due to the reduced number of vessels we are operating and the ongoing downturn in business, we are beginning consultation proceedings with a proposal to make around 1,100 of our colleagues redundant."
Jobs are at risk across all levels of the business, owned by DP World, which is based in Dubai.
It emerged in early April that P&O Ferries was seeking a £150 million bailout from the UK Government to avoid collapse, but no offer was made.
The PA news agency understands that the firm's proposal was based on running its full complement of 21 ships.
But the company is now only operating 15 vessels, with reduced frequency, and expects to reach an agreement with the Government for a lower amount of money to secure critical supply routes.
It emerged last month that DP World was set to pay shareholders a £270 million dividend.
A source told PA the firm was legally required to make the payment.
P&O began operating ferries in the 1960s.
Before the pandemic, its ships carried 8.4 million passengers on 27,000 sailings a year across the Channel, North Sea and Irish Sea.
Mick Cash, general secretary of the RMT union, said: "This is devastating news and an appalling betrayal of the P&O workforce.
"This is a kick in the teeth for P&O seafarers who have maintained key supply lines to the UK during the Covid-19 pandemic.
"What is utterly shameful is P&O have been kept afloat by our members and the taxpayer whilst their owners have been paying out hundreds of millions in dividends in Dubai and cooking up plans to permanently replace UK seafarers with low-cost seafarers from thousands of miles away.
"This is an attack on British seafarers, crew and the biggest fear is that these jobs will never return to Dover or Hull.
"But you can guarantee that P&O ferries will still be running passenger ferry services from those ports to protect their owner's profits at the country's expense.
"We are seeking urgent talks with the company and will fight tooth and nail against these job losses and we are calling on the Government to step in now and nationalise these services to protect jobs and the UK's maritime interests."
