Boris Johnson has said he takes “personal responsibility” after his Conservative Party lost the North Shropshire by-election in a shock result that has dealt another significant blow to his premiership.

Lib Dem candidate Helen Morgan overturned a huge Tory majority to triumph in the contest, which was sparked by the resignation of Owen Paterson amid a lobbying scandal.

Speaking to broadcasters following the result, the prime minister said: “I am responsible for everything the government does and of course I take personal responsibility.

“Clearly the vote in North Shropshire is a very disappointing result and I totally understand people’s frustrations, I hear what the voters are saying in North Shropshire and in all humility I have got to accept that verdict.”

Conservative co-chairman Oliver Dowden earlier admitted that his party had been given “a kicking”, telling Sky News that voters in North Shropshire wanted to send “a message” that “we have heard that loud and clear”.

Meanwhile, veteran Tory MP Sir Roger Gale warned the prime minister that he has “one more strike” left after a series of setbacks in recent weeks.

Live updates as the Conservatives lose North Shropshire to the Liberal Democrats

Mrs Morgan polled 17,957 votes, ahead of Tory candidate Neil Shastri-Hurst on 12,032, giving her a majority of 5,925.

Labour’s Ben Wood was a distant third with 3,686 votes.

Asked which things going wrong under his watch were to blame for the defeat, the PM told broadcasters that “what the people have been hearing is just a constant litany of stuff about politics and politicians and stuff that isn’t about them and isn’t about the things that we can do to make life better”.

The PM added that he needs to “fix” issues like the reported Number 10 parties and the funding of the refurbishment of the No 10 flat.

“Those questions are exactly the kind of questions about politics and politicians and all those kind of things, the running of government, that I’m going to have to fix of course,” he said.

Sir Roger Gale said the Tories’ North Shropshire by-election defeat should be seen as a “referendum” on Mr Johnson’s premiership and described it as “not a happy day for the prime minister”.

“I thought it was highly likely that this would happen. I do not want to detract from Helen Morgan’s very considerable victory, but this wasn’t a vote for the Liberal Democrats, this was, effectively, a referendum on the performance coming out of Downing Street at the moment,” he told Sky News.

“He has got good fortune of having the House in recess. The House has got time to think about this, the party has got time to think about this. He has got about three weeks now to regroup and he is going to have to do that very fast indeed.

“We have had two strikes – first of all, the Conservative Party in the House of Commons earlier this week, now this result. One more strike and I think he is out.”

Analysis: By-election ‘drubbing’ will send shockwaves through the Tory party

Sir Roger also confirmed he has already written a letter to the Conservative 1922 Committee of backbench MPs but does not know how many more of his colleagues have.

“I would not be a bit surprised if people didn’t start to write some of those letters,” he told Sky News.

He added that it is “quite possible” that “there might be a protest vote” in the Southend by-election in the New Year – despite both Labour and the Liberal Democrats agreeing not to stand due to the circumstances of former MP Sir David Amess’ death.

“This is not a happy time for the prime minister, I am afraid.”

Fellow Conservative Sir Geoffrey Clifton-Brown said Mr Johnson needs to “go away for Christmas, come back in the new year, deal with these self inflicted own goals and then start to deliver on the really biggest issues for the country that the electorate want”.

Mr Clifton-Brown told Sky News he is giving the prime minister “the benefit of the doubt” at the moment, but stressed he must “work out how he can conduct himself and govern this country in a way that avoid these sorts of issues”.

In Mrs Morgan’s victory speech, the Lib Dems’ 13th MP said voters in North Shropshire have “spoken on behalf of the British people” and told Mr Johnson “loudly and clearly” that “the party is over”.

Mrs Morgan later used a yellow pin to pop a large blue balloon which had “Boris’ Bubble” emblazoned on the side.

But speaking to Sky News on Friday morning, Mr Dowden told Sky News that the PM is still an “electoral asset” to the Conservative Party and has the “drive and determination” to lead.

He added that while he does not know how many letters of no confidence may have been submitted to the Conservative 1922 Committee, he still has “every confidence” in Mr Johnson.

“Just take the three really big calls we’ve faced. Get Brexit done: he’s delivered on it. We’ve delivered the fastest booster programme in the world twice over and we’ve seen the economy through this terrible period, with unemployment lower than when we entered,” he said.

But Lib Dem leader Sir Ed Davey described the win as “a watershed moment in British politics”.

He said many people who voted for his party in North Shropshire were individuals who “played by the rules, who used to vote Conservative”.

Earlier this week, 100 of the prime minister’s own MPs rebelled over COVID passes, by far the biggest mutiny of his premiership.

There have also been allegations of rule-breaking over numerous Christmas gatherings last year at a time of heightened COVID restrictions, further scrutiny of the refurbishment of the PM’s Downing Street flat and questions about his leadership more generally amid Labour taking the lead in a number of opinion polls.

The North Shropshire result is another headache for Mr Johnson and comes as his government battles the Omicron variant of COVID-19 and weighs whether to impose further restrictions amid its continuing spread.