Theresa May's national security adviser Sir Mark Lyall Grant is to retire in April.
Sir Mark, 60, will be replaced by Mark Sedwill, the mandarin currently in charge of the Home Office.
The Prime Minister said Sir Mark had made a "huge contribution" but Mr Sedwill was "ideally qualified" to take up the role.
Career diplomat Sir Mark served as the UK's ambassador to the United Nations before taking over the national security adviser role.
Mrs May said: "I would like to thank Mark Lyall Grant for his long years of public service, in the Foreign and Commonwealth Office, at the United Nations and also in particular for his work since 2015 as national security adviser. Mark has made a huge contribution and I wish him every success for the future."
Mr Sedwill also has extensive Foreign Office experience and was the prime minister's special representative for Afghanistan and Pakistan before taking up the role as permanent secretary in the Home Office in 2013, when Mrs May was home secretary.
The Prime Minister said: "Mark Sedwill's experience means that he is ideally qualified to take up the critically important role of national security adviser.
"As well as his recent time in the Home Office, he has served in both Afghanistan and Pakistan and has wide-ranging experience of foreign and security policy issues."
Sir Mark will leave the civil service on April 13 and his retirement will trigger a series of changes in Whitehall's senior roles.
Mr Sedwill will be replaced at the Home Office by Philip Rutnam, who moves from the Department for Transport.
A Civil Service Commission-led competition has been launched to find a successor to Mr Rutnam, with senior DfT official Jonathan Moor acting as permanent secretary until a successor is in place.
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