The network, which broadcasts Gogglebox and The Great British Bake Off, will lose around 28% of its current 1,270 staff following a strategic review of the organisation.
Priya Dogra, Channel 4's chief executive, said the announcement "marks the first phase of our transformation, ensuring Channel 4 is the right shape and size to deliver its future strategy and focus investment in the programmes audiences love".
Caroline Dinenage, chair of the culture, media and sport committee said the news would be "deeply worrying for the talented and dedicated people who work at Channel 4".
The network said it planned to focus on creating a simpler and more efficient operating model and enable greater investment in distinctive programming.
In her statement, Dogra said: "Channel 4 is 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.
"The challenges we face require a fundamental transformation in how we work. I know the proposals we are announcing today will be very difficult for many colleagues and will have a significant impact across the organisation. "
She added: "These decisions have not been taken lightly, but I strongly believe they are necessary to create a simpler, more focused and more sustainable Channel 4. "
The company referenced the rapidly changing media landscape , external announcing the changes, which it said includes "evolving audience habits, increasing global competition, a challenging consumer environment and a volatile advertising market".
One of Channel 4's biggest hits, Married at First Sight, is also currently off air uncovered allegations of rape and other serious misconduct.
The announcement about job cuts represent the biggest round of layoffs in the history of Channel 4, which launched in 1982.
, external Dogra told employees on Wednesday that the redundancies will ensure that more of Channel 4's £1bn income is spent on screen.
A consultation process with staff will begin shortly, and Channel 4 said its "future strategic direction is well advanced and will be shared in the coming months".
In her statement, Dinenage said: "There are questions about what the announcement means for the broadcaster's presence in the regions, one of its success stories of recent years.
"Channel 4 is a unique asset and must find ways to maintain independence and distinctiveness while capitalising on efficiencies and opportunities for collaboration. "