It follows reports that President Trump was outraged by comments made by Mulvaney during the Ukraine corruption saga.
The allegations of abuse of power over the Ukraine incident led to impeachment proceedings against President Trump.
Mulvaney's departure has been on the cards for the last few weeks.
Mr Mulvaney is to become US special envoy to Northern Ireland, while North Carolina lawmaker Mark Meadows has been appointed to take over his former position.
Lebanon, Israel conclude US-brokered talks in Rome
Lebanon and Israel concluded US-brokered talks in Rome on Wednesday, with a US official saying they had made progress on implementing a plan that could see Israeli forces begin to withdraw from some parts of southern Lebanon within days.
US launches new round of strikes against Iran
The US conducted a new wave of strikes against Iran's coastal defence systems and missile sites on Wednesday after reimposing a naval blockade of Iranian ports.
Zelenskyy endorses energy boss as new Ukraine prime minister
President Volodymyr Zelenskyy endorsed the head of the state energy company on Wednesday to be Ukraine's new prime minister, while giving no clear answer on the future of the defence minister at a pivotal juncture in the war.
Trump resumes Iran port blockade, threatens strikes on energy targets
President Donald Trump has reimposed a naval blockade of all Iranian ports on Tuesday and threatened to hit power plants and bridges next week unless Tehran resumes negotiations as the US military completed another round of strikes on Iran.
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