Ben Wallace says he will step down as defence secretary at the next Cabinet reshuffle after four years in the job.
He told the Sunday Times he would not stand at the next general election, but ruled out leaving “prematurely” and triggering a by-election.
Mr Wallace has served as defence secretary under three prime ministers and has played a high-profile role in the UK’s response to the Ukraine war.
Sources told the BBC they expect the next reshuffle in September.
Rishi Sunak is reportedly planning to shake up his top team, but no date has been confirmed.
Mr Wallace said he was quitting frontline politics due to the toll it had taken on his family, and allies of his have said the decision was not a reflection on Mr Sunak’s leadership.
His Wyre and Preston North constituency is set to disappear at the next election under upcoming boundary changes and he told the newspaper he would not seek a new one.
The 53-year-old’s confirmation of his plans to the Sunday Times comes after days of speculation that he was considering leaving government.
He has always been popular with Tory party members and his decision is likely to be seen as quite a blow for the party by some Conservatives.
It also leaves a big vacancy in government, which Rishi Sunak will have to fill.
Last week, the prime minister disowned comments from Ben Wallace in which he suggested Ukraine should show more “gratitude” for the military support it has been given.
The comments were made at a fringe event at the Nato summit in Vilnius, after Ukraine’s president Volodymyr Zelensky said it was “absurd” that Nato would not give a timetable for his country securing membership of the bloc once the war with Russia is over.
On Twitter on Saturday evening, writing in Ukrainian, Mr Wallace said his comments had been “somewhat misrepresented”, and he was making the point that in some parliaments there “is not such strong support as in Great Britain”.
He said his comments had not been about governments but “more about citizens and members of parliaments”.
He noted the strong support for Ukraine amongst the British public, and added he would “continue to support Ukraine on its path for as long as it takes”.
The BBC understands Mr Wallace informed the prime minister on 16 June of his decision to stand down from the Cabinet.
Ben Wallace, a former soldier, told the Sunday Times: “I went into politics in the Scottish parliament in 1999. That’s 24 years. I’ve spent well over seven years with three phones by my bed.”
He suggested in the interview that he would continue to call for higher defence spending, something he has campaigned for throughout his time in the role.
It comes weeks after Mr Wallace said he was no longer in the running to be the next secretary general of Nato, a role he was widely reported to be seeking.
The announcement that Jens Stoltenberg would be continuing in the job effectively ended his hopes of becoming the next head of the military bloc.
Mr Wallace has played a vocal role in supporting Ukraine, including overseeing the transfer of weapons and vehicles to its army.
His position as defence secretary, when Russia launched its full-scale invasion of Ukraine, saw his profile increase at home and abroad.
Mr Wallace has served longer in the role than any Conservative defence secretary before him, but told the Sunday Times he was conscious of the impact the job has had on his family.
Mr Wallace told the newspaper: “While I am proud to have worked with so many amazing people and helped contribute to protecting this great country, the cost of putting that ahead of my family is something I am very sad about.”
Before entering politics as a member of the Scottish Parliament in 1999, Mr Wallace served in the Army as an Officer in the Scots Guards.
He was first elected to the Commons in 2005, and previously served as a minister in the Northern Ireland department and in the Home Office.
What is next for him is unclear.