Labour has won an easy victory in the Stretford and Urmston by-election in a boost for Keir Starmer.
Andrew Western, the Labour leader of Trafford Council, was the winner with a majority of 9,906 - and a swing from the Tories of 10.5%.
It is another blow to Rishi Sunak, who suffered a humiliating defeat at a City of Chester by-election when Labour increased its majority by more than 4,000 votes only two weeks ago.
New MP Mr Western said the result sent a "strong message" to Mr Sunak's Government.
"The people of Stretford and Urmston do not just speak for this constituency but for millions more people up and down the land who know that this government has been letting us down for the past 12 years," he said.
"The Tories have given up on governing and it is increasingly clear that the British people are giving up on them."
Polling expert Prof Sir John Curtice said the Tories would "definitely lose" the next election if the 10.5% swing was repeated.
He said Labour would still be "somewhat short" of an overall majority in the Commons based on the swing alone - but added the seat was already a safe red one so a huge swing was always unlikely.
He told the BBC: "If you take Stretford and Chester together, they basically are consistent with the evidence of the opinion polls.
"[That] is Labour are now in a stronger position than they have been at any point since David Cameron first walked through 10 Downing Street as prime minister in 2010.
"Therefore, the challenge of the Conservatives are facing is certainly a very substantial one."
The by-election was triggered by the resignation of Labour's Kate Green, who formally quit as an MP last month to become Andy Burnham’s deputy mayor of Greater Manchester.
Voters headed to the polls in the Greater Manchester seat yesterday as nine candidates battled to succeed Ms Green.
Bitterly cold conditions on polling day and the expectation of an easy Labour hold contributed to turnout of just 25.8%
Mr Western secured 69.65% of the votes, up 9.34% on the snap general election three years ago, and with a 10.5% swing from Conservatives to Labour.
He said it was "clear... that people are ready for a Labour government, and let the message go out tonight that Labour are ready to govern".
Mr Western said the by-election "must hold the record for the coldest polling day" and thanked voters who went out to back him.
"It's clear from the result, and from the conversations I have had with voters throughout the campaign, that the public want a General Election," he said.
"The Conservative Party are failing to lead the country. They have unleashed a wrecking ball through the foundations of our economy and undermined the public's trust in democracy."
Tory candidate Emily Carter-Kandola came in second with 2,922 and a 15.86% share of the vote.
Ms Green, a former shadow education secretary, held the constituency with more than 60% of the vote - a majority of 16,417 - in 2019 after being first elected in 2010.
The Tories came second at the last election, with the Lib Dems in third.
The result comes after a string of positive polls for Labour, with pressure mounting on the Government over the cost-of-living crisis, soaring inflation and nationwide strikes.
Declining support for the Tories was made clear at the by-election in Chester, triggered by the resignation of Labour MP Christian Matheson after complaints of serious sexual misconduct were upheld.
At the time of the result, Deputy Leader Angela Rayner said Mr Sunak had "failed" and the Tories had taken a "pelting" after new MP Samantha Dixon increased Labour's majority by more than 4,000 votes.
A bombshell poll by Savanta and Electoral Calculus recently predicted a 314-seat majority for Labour with the Tories losing every seat north of Lincolnshire.
Mr Starmer's party would win 482 seats if a general election was held tomorrow, the eyebrow-raising forecast said, more than double the 202 they hold now.
The other most recent by-elections, which took place on the same day in June, were a disaster for the Conservatives - with Labour snatching Wakefield and the Liberal Democrats securing a historic victory in Tiverton and Honiton.
