Zac Goldsmith has resigned as a Tory MP in protest at the decision to allow a third Heathrow runway, which he called "catastrophic".
The move will trigger a by-election in his Richmond Park constituency, but the Conservative Party has said it will not put forward another candidate.
Sky's Chief Political Correspondent Jon Craig said the Tories were worried about splitting the vote and the Lib Dems clinching the seat.
Mr Goldsmith, who was a backbencher, is therefore likely to stand as an independent and return as the constituency's MP.
The election in south-west London could be held as early as December.
A Conservative spokesman said the party "understood" Mr Goldsmith's decision and called him a "hard-working champion" for his constituents.
After the decision to expand Heathrow was announced, Mr Goldsmith stood up in the Commons to tell MPs it was "catastrophic".
He added: "The Government has chosen a course that is not only wrong, it's doomed."
Mr Goldsmith is a well-known environmentalist whose wealthy London constituency is under the Heathrow flight path, with planes regularly flying low over the area.
He said people felt let down by David Cameron's promise in 2009 that "no ifs, no buts" the runway would never be built.
Speaking on Tuesday evening at his constituency office, Mr Goldsmith said: "I told you that if my party changed its position, I would trigger a by-election and give you a chance to vote again.
"There was no small print. No expiry date. No ambiguity. It was a simple promise. And it mattered. I know it mattered, because the thought of Heathrow expansion fills most of my constituents with dread.
"That's why my party's promise mattered. It's why my promise mattered. And it's why so many people in our community feel so let down today."
Mr Goldsmith said the project would be a "millstone" around the Government's neck and would never be completed because of "complexity, cost and legal difficulties".
After his press conference, he told Sky News: "People here feel as strongly as I do about the issue.
"You can have a referendum about Heathrow and you will get Zimbabwean-esque results.
"Almost everyone is opposed. It has massive massive implications, way beyond Richmond Park. It affects a million people, it's a significant chunk of our population.
"I don't believe Heathrow will be delivered. I see this by-election as a referendum on Heathrow."
The Government's decision to back Heathrow over Gatwick - which promised a cheaper and quicker project - has also drawn scorn from members of the Cabinet.
Foreign Secretary Boris Johnson called it "undeliverable" and Education Secretary Justine Greening said it was "disappointing".
The Prime Minister Theresa May however said it was the right decision for Britain and "vital for the economic future of the whole of the UK".
Transport Secretary Chris Grayling said the Government had "thought long and hard" about where to build the runway.
He said Heathrow was "best for the whole country - to create better connectivity to the regions of the UK and the best trade links to the world".
Mr Grayling added: "We've taken the view that where people have direct constituency concerns and interests they should have the freedom to articulate those long-held views."
Work on the £17.6bn runway project is expected to start in 2021, with flights taking off from 2025.
The Government has attached conditions including a six and a half hour night-flight ban, more stringent noise conditions and a £2.6bn compensation fund for residents.