Prime Minister Rishi Sunak faces a triple by-election threat as votes are counted in contests which will be viewed as a test of his leadership.
Less than two hours after polls closed, the Liberal Democrats claimed they had “romped home” in Somerton and Frome, overturning a Tory majority of more than 19,000.
In Uxbridge and South Ruislip, and Selby and Ainsty, Labour hopes to take the constituencies, although the party said “they were always going to be a challenge”.
A triple defeat for the Tories would heap pressure on the Prime Minister ahead of a general election expected next year.
While Labour and the Tories attempted to manage expectations, the Lib Dems were jubilant.
A Lib Dem spokesman said: “We’ve not just won, we’ve romped home in Somerton and Frome.
“The Conservative vote is in freefall.”
Party leader Sir Ed Davey joked: “I think we’re going to need a bigger tractor.”
If the Lib Dem prediction is correct, Sarah Dyke will become the next MP for Somerton and Frome, defeating Tory candidate Faye Purbrick.
Losses for the Tories in all the contests would be the first time in 55 years that a government has been defeated in three by-elections on the same day.
The Uxbridge and South Ruislip vote was triggered by the resignation of former prime minister Boris Johnson, who held the seat with a majority of 7,210 as he led the party to a national landslide in 2019.
In Selby and Ainsty the by-election follows the resignation of Mr Johnson’s ally Nigel Adams, who had a majority of 19,213.
A Conservative spokesman said: “There’s no doubt that this was always going to be a very challenging set of by-elections, especially given the circumstances in which they were brought about.
“We have to wait for the results to come in, but by-elections are rarely won by governing parties and they are rarely good indicators of general election performance.
“Across all of these campaigns we have heard zero enthusiasm for Sir Keir Starmer’s Labour Party and their lack of answers.
“We now need to redouble our efforts earning back the trust of voters by delivering on our plan to halve inflation, grow the economy, reduce debt, cut waiting lists and stop the boats.”
The Prime Minister could attempt to reset his administration with a Cabinet reshuffle in the wake of the contests – Defence Secretary Ben Wallace has already signalled he will exit the Government so there is a vacancy to be filled – although No 10 has publicly said there are no plans for a shake-up.
Mr Sunak may decide the benefits of freshening up his team at this stage would be outweighed by the risk of it being perceived as a panicked response to an electoral setback.
In Uxbridge and South Ruislip, Labour’s Danny Beales hopes to defeat Tory Steve Tuckwell, although rows over the Mayor of London Sadiq Khan’s decision to extend the Ulez low emission zone may cost Labour votes.
Labour insiders admitted it was very tight in the west London seat, with the prospect of a £12.50 daily Ulez charge for cars which fail to meet the emissions threshold a factor dampening the party’s vote.
The Tory MP for neighbouring Ruislip, Northwood and Pinnder David Simmonds told the PA news agency that people had been asking “what will be the impact of the Ulez” and other local issues.
Mr Simmonds said “Clearly we are going to find out tonight how the voters weigh that in the balance against some of the broader concerns they may have about things like the cost of living and the impact of global events that we felt in our UK economy.”
In Selby and Ainsty, Keir Mather, 25, will become the new Baby of the House if he wins for Labour, with Tory Claire Holmes trying to retain the seat for her party.
Labour chairwoman Anneliese Dodds played down expectations after the polls closed, calling them “incredibly challenging elections” for the party.
She also told BBC Newsnight: “Whatever the result one thing is very clear, and it’s been clear to me when I’ve been speaking with people on the doorstep that there will be people in this election who will be voting Labour for the first time.
“They can see that Keir Starmer has turned the Labour Party around, that the Labour Party is in the service of working people.
“And I think that will definitely be the case whatever the eventual result from these by-elections.”
Tory MP Andrew Jones said the result in the Selby and Ainsty constituency would be “close”, pinning the blame on Mr Adams’ resignation.
“The sitting MP walking away has been a sense of disappointment and that’s putting it quite mildly,” he said.
