William Hague has rejected suggestions that ex-defence secretary Liam Fox and his friend, the lobbyist Adam Werritty, may have been independently trying to create foreign policy.
The idea that one minister could run a "completely separate policy is a fanciful idea", the foreign secretary told BBC One's Andrew Marr show.
Mr Fox had co-operated with the Foreign Office on policy, Mr Hague added.
His remarks come as ministers consider a statutory register of lobbyists.
Government sources have told the BBC the government is to consult later in the year on a register, with legislation expected by next year.
Meanwhile, the City of London police are consider investigating Mr Werritty for fraud for using business cards falsely claiming he was an adviser to Mr Fox.
Mr Fox resigned from his cabinet post on Friday after a week of damaging headlines over his working relationship with Mr Werritty, his former flatmate and best man.
It emerged that Mr Werritty had met Mr Fox 22 times at the Ministry of Defence and joined him on 18 overseas trips since he came to office last year - despite having no official role.
Mr Werritty was present at meetings Mr Fox had with military figures, diplomats and defence contractors.
Asked about fresh, unconfirmed allegations relating to Mr Werritty dealing with Iranian exiles and discussing the overthrow of the Ahmadinejad regime, Mr Hague said that, in his experience, Mr Fox had always co-ordinated with him and the Foreign Office.
"If I asked him not to go to Sri Lanka, then he didn't go. Or if I asked him when he went to convey messages of the government, messages from me then he conveyed those messages."
He added: "The foreign policy of this country is set by me, the prime minister working through the National Security Council, pursued by 140 ambassadors in 260 embassies and consulates - it's a huge operation.
"One adviser or non-adviser, whatever he may have been to one minister, isn't able to run a totally different policy from the rest of the government. And I think people can at least be reassured about that."
Mr Hague said he had not come across Mr Werritty since becoming foreign secretary, but did meet him while in opposition.
In recent days, attention has centred on Atlantic Bridge, the now-defunct charity founded by Mr Fox.
Mr Hague, who was on the advisory council, spoke at an event in the US.
He said the organisation promoted transatlantic links and there was nothing "sinister" about it.
Meanwhile, questions are continuing to be asked about who paid for Mr Werritty's business activities and whether he had personally benefited from his frequent access to the defence secretary.
On Friday, venture capitalist Jon Moulton said Mr Fox approached him after the election seeking funds for Pargav - a non-profit company set up by Mr Werritty involved in "security policy analysis and research".
The Sunday Telegraph reported that some of the rich company donors were furious at being drawn into the row and had complained they were misled about the use of funds.
Mr Fox's conduct is being investigated by Cabinet Secretary Sir Gus O'Donnell.
His report is due to be published on Tuesday, Mr Hague said.
He added that the prime minister would then consider what action to take, in particular over the role of lobbyists.
'Cleaning up politics'
International Development Secretary Andrew Mitchell said the prime minister and the cabinet secretary would look at what lessons could be learned.
Mr Cameron was committed to "cleaning up politics," he told Sky News's Murnaghan programme, adding: "We make a virtue of openness."
Shadow Defence Secretary Jim Murphy has called for a wider inquiry, once the initial report is published.
"It's now clear that there are much wider issues at stake: access to money; access to influence; money off the books; money undeclared influence. And I think what we need to do is follow the money trail and see where it leads us," he told BBC One's Politics Show.
Writing in the Observer, Mr Murphy also accused Mr Werritty of treating Mr Fox as "a franchise to bolster his income".
Mr Werritty has been interviewed by civil servants working on the report but has not spoken to the media.