Former Conservative MP Zac Goldsmith has taken a 27 point lead over the Liberal Democrats as the Richmond Park by-election campaign kicks off.
A BMG Research poll for The Evening Standard, of 543 people in the West London seat, found 56% (-2) of voters backed Goldsmith, while 29% (+10) supported Liberal Democrat hopeful Sarah Olney.
The vote was triggered after Goldsmith quit the House of Commons over the government's decision to back a third runway at Heathrow Airport. The environmentalist will stand as an independent on an anti-Heathrow ticket.
But Olney and the Liberal Democrats are also opposed to expanding the West London site.
Their stance means the election could be another vote on the EU, since Goldsmith backed a Brexit and 69% of Richmond-upon-Thames residents voted Remain at the 23 June ballot.
"If people see it as an opportunity to send a message on Heathrow then I will be given a big mandate and the government will have to take heed," Goldsmith told the Standard.
"But if I'm squeezed or booted out, the risk is exactly that, the consequence of that risk is Heathrow will take heart. If I'm sent back with a diluted mandate, or not sent back at all, then Heathrow will be licking their lips."
The Conservatives and Ukip have decided not to contest the seat, while the Greens are currently considering whether to field a candidate.
Insurance tycoon Arron Banks, a Ukip donor and co-founder of Leave.EU, told IBTimes UK his Eurosceptic group would support Goldsmith.
Labour will field a candidate, despite shadow ministers Clive Lewis, Lisa Nandy and Jonathan Reynolds warning against such a move. The vote is expected on 1 December.