Libyan Foreign Minister Moussa Koussa is in Britain and "no longer willing" to work for Libyan leader Muammar Gaddafi's regime, the Foreign Office says.
He flew into an airport near the capital earlier on Wednesday.
He has subsequently spent hours talking to British officials.
His apparent defection comes as rebels in Libya are retreating from former strongholds along the eastern coast as Colonel Gaddafi's forces advance.
The rebels have now lost the key oil port of Ras Lanuf and the nearby town of Bin Jawad, and are also in full retreat from Brega. In the west, the rebel-held town of Misrata is still reportedly coming under attack from pro-Gaddafi troops, reports say.
'Own free will'
A British Foreign Office spokesperson said: "We can confirm that Moussa Koussa arrived at Farnborough Airport on 30 March from Tunisia. He travelled here under his own free will.
"He has told us that he is resigning his post. We are discussing this with him and we will release further detail in due course.
"Moussa Koussa is one of the most senior figures in Gaddafi's government and his role was to represent the regime internationally - something that he is no longer willing to do.
"We encourage those around Gaddafi to abandon him and embrace a better future for Libya that allows political transition and real reform that meets the aspirations of the Libyan people."
A senior US administration official, speaking to AFP News agency on condition of anonymity, said: "This is a very significant defection and an indication that people around Gaddafi think the writing's on the wall."
Earlier, British Foreign Secretary William Hague announced that five Libyan diplomats were being expelled from the country.
He told MPs that the five, who include the military attache, "could pose a threat" to Britain's security.