The broadcaster said it had done a “comprehensive review” earlier in the year and found a need for a “change in how the organisation operates”.
It said its new structure would “greatly reduce non-programming spend” and reduce management layers, simplify decision-making and remove duplication.
The changes come nearly two years after it axed 200 roles under Alex Mahon’s leadership.
Current Channel 4 chief executive Priya Dogra – who joined from Sky in March – said the broadcaster was a “precious asset which plays a unique role in the UK”.
“We need to secure and own our future so we can continue to make shows others won’t, reach audiences others can’t, and thrive as a distinctive and disruptive British voice for future generations,” she said.
Ms Dogra said Channel 4 needed a “fundamental transformation in how we work” to deliver programmes audiences want to watch and “deliver its future strategy”.
She added: “I know the proposals we are announcing today will be very difficult for many colleagues and will have a significant impact across the organisation. Many talented people who have made an enormous contribution to Channel 4 will be leaving as a result.”
The cuts equate to 28% of the company’s workforce.
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Ms Dogra said the job losses had not been taken lightly but were needed “to create a simpler, more focused and more sustainable Channel 4”.
Channel 4’s chair, Geoff Cooper, said it would mean a “more sustainable and resilient organisation” that could maximise investment in content.
A formal consultation with staff over the cuts will take place and the broadcaster said more details on its future strategy would be shared in the coming months.
