Liberal Democrat challenger Sarah Olney, whose centrist party wants a second referendum on Brexit, is hoping the result will send shockwaves through Downing Street as the government presses on towards the EU exit door.
Olney is running against Zac Goldsmith, who held the seat for Prime Minister Theresa May's Conservative Party but quit in protest after the government backed expanding the nearby Heathrow Airport.
He is now standing as an independent candidate.
"While some people feel very strongly about Heathrow expansion, lots more people feel much more strongly about Brexit," Olney told AFP during the campaign.
"That's really alarmed and upset people and they want to use this opportunity to send a message."
The Lib Dems say a shock result would force the government to think again about pursuing a so-called "hard Brexit" divorce from the European Union.
The political blog Labour List called it the "Brexit by-election".
In the June referendum on Britain's EU membership, 52 per cent nationwide voted to leave, but in Richmond, a well-heeled borough in southwest London, 69 per cent voted to remain in the bloc.
Its 82-per cent turnout, one of the highest in the UK, showed it was an issue locals felt passionate about.
The unambiguously pro-EU Lib Dems, reduced to a rump presence in parliament in the 2015 general election, are eyeing a comeback by filling the void for disgruntled "Remain" voters.
Irish rocker-turned-activist Bob Geldof, a prominent Remain campaigner, weighed into the by-election to drum up support for Olney on yesterday -- despite being an old friend of Goldsmith.
"We lost the battle but really the war hasn't begun," he said, calling Richmond Park the start of a "fightback" following the Brexit vote.
But he was heckled by some locals.
Olney, 39, faces a tough task in beating Goldsmith, who won Richmond from the Lib Dems in 2010 and retained it in the May 2015 general election with 58 per cent of the vote.
Both the Conservatives and Brexit-cheerleaders UKIP have opted out to give him a clear run, and bookmakers William Hill said Goldsmith had a three in four chance of retaining the seat.
However, The Guardian newspaper reported yesterday that it had seen Lib Dem internal data predicting Olney will win 47 per cent of the vote and Goldsmith 46 per cent.
Six other candidates are standing.
(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)