Officials insisted that Simmonds' decision was unrelated to that of Sayeeda Warsi, who quit last Tuesday in protest at the government's failure to take a tougher line against Israel over its assault on Gaza.
Simmonds had decided "some weeks ago" to leave but agreed to stay to chair a UN meeting on the Democratic Republic of Congo last Thursday, a spokesman for Prime Minister David Cameron's Downing Street office said.
In his resignation letter, Simmonds said he was "exceptionally proud" of the government's achievements but said he wanted to spend more time with his family, and will be leaving parliament at the general election next year.
"There's nothing suspicious about this resignation -- there's no difference between myself and the government on policy," the outgoing minister later told the BBC.
Despite the apparently amicable nature of his departure, it will be seen as a blow for the Foreign Office as it adapts to an overhaul of ministerial staff at a time of numerous international crises.
Philip Hammond replaced William Hague as foreign secretary -- the top job -- in a reshuffle last month, which also saw Middle East minister Hugh Robertson replaced.
Of the seven ministers now at the Foreign Office, four have been in their post less than a month.
In her resignation letter last week, Warsi praised Hague but said there was "great unease across the Foreign Office, amongst both ministers and senior officials, in the way recent decisions are being made".
The peer, Britain's first Muslim cabinet member who also had responsibility for faith and communities, said the government's policy on Gaza was "morally indefensible".
In an ITV news interview on Monday, Hammond stressed the two resignations were entirely different.
"Mark Simmonds agreed with the prime minister at the time of the reshuffle that he wanted to stand down -- he wants to stand down from parliament at the next election," he said.
"Baroness Warsi's departure is in a different category altogether."
Simmonds has been Conservative member of parliament for Boston and Skegness in eastern England since 2001 and was appointed to the Foreign Office in September 2012.
He had responsibility for Africa, Britain's overseas territories, the Caribbean, as well as climate change and international energy.
His replacement is James Duddridge, a Conservative MP and party whip who previously served on the House of Commons international development committee.
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and who says the real cause is not personal??? we are not talking about Pakistan where it is unheard of that a politician ends his or her career after a good run to spend time with the family. Looking after family is more than looting and amassing people's money in own bank accounts and hogging the chairs till death, as is customary in Pakistan. Politicians take these decisions regularly in the more decent government systems around the world.
Saeeda Warsi was at least wasn't dishonest and didn't leave any ambiguity while resigning. Mark Simmonds could be more clear in his resignation and let the BBC not hide the real cause.