The former Conservative MP for Corby, Louise Mensch, has insisted Labour's by-election victory "is not going to mean anything" for the PM's leadership.
Mrs Mensch said she "took the blame" for the Conservative loss, after deciding in August to leave her seat and move to New York with her family.
Labour's Andy Sawford won the seat by 7,791 votes in Thursday's by-election, with the Tories second and UKIP third.
Mr Sawford said the win was a "damning verdict" on David Cameron's leadership.
The last time Labour took a seat from the Conservatives in a by-election was at Wirral South in February 1997.
Speaking to BBC Newsnight, Mrs Mensch said she "absolutely" was responsible for the Conservative defeat, but added she had to resign "to be with my family".
"The prime minister was very good about letting me work my schedule around my children... but because my husband lived in America we were facing a possible 13-year separation from each other."
'Run of the mill'
She said she believed the swing to Labour was a "very respectable result" for the Tory Party, given the nature of her resignation.
"We've seen over and over again even safe seats change hands against the governing party in a by-election and that's when they didn't have to contend with the sitting MP leaving for family reasons.
"Under those circumstances to get a 12% swing is pretty run of the mill, so I don't think that it's anything we can draw wider lessons from," she said.
Mrs Mensch denied she had left the role because she was worried about her popularity in the polls, and again insisted she had not told her husband Peter that she "would get killed at the next election".
She also dismissed suggestions she had left because her political career was not advancing quickly enough.
"Contrary to massive public rumour I never wanted to be a minister.
"I had small children to look after and spent two days a week in my constituency at weekly surgeries. I could never have done it in the first place and I never wanted to."
Mrs Mensch won the Northamptonshire seat at the 2010 general election with a majority of less than 2,000 votes, and Labour had been widely tipped to take the seat.
Labour took 17,267 votes, in a 12.67% swing from the Conservatives, who took 9,476, which if repeated a general election would give the party a 100 seat majority.
UKIP came a comfortable third with 5,108 votes and the Liberal Democrats fourth with 1,770.
Some 35,733 votes were cast in Corby, giving a turnout figure of 44.8%.
In his victory speech, Mr Sawford said "Middle England" had sent a "very clear message" to Mr Cameron, and added that the win was a "damning verdict" on the prime minister and the Conservatives' "betrayal of the British people".
Referring to Corby's status as a classic swing seat, he claimed "the road to Downing Street runs through Corby".
In response, Mr Cameron said: "It's a classic mid-term result and obviously made difficult by the fact that the Conservative MP left the seat in question.
"What the government needs to do is keep going with the very important plans we have to get our economy and country back on track."