UKIP leader Nigel Farage has warned David Cameron and Ed Miliband "we're after you" after the party claimed its first elected MP by winning 12,404 votes in the Clacton by-election.
Elsewhere, the party slashed Labour's majority in Heywood and Middleton to just 617 votes, which Mr Farage hailed an "absolutely astonishing" result.
Former Conservative MP Douglas Carswell won a landslide victory in Clacton, Essex, by securing 21,113 of the 35,386 votes cast.
UKIP also forced a recount in Heywood and Middleton, where Labour's Liz McInnes narrowly defeated UKIP's John Bickley.
Mr Farage said the results showed UKIP was now "a truly national party - indeed we are the only party that can challenge in solid Tory and Labour areas".
Video: No Complacency From Labour
He went on: "I've no doubt we'll hear, 'it's just a protest vote'. It's nothing of the kind. People from across the spectrum are saying. 'we've had enough of career politics'. They want to have a proper voice in Westminster.
"From today with Douglas Carswell they have got one, and in a few weeks time I believe they will have another in the shape of Mark Reckless, with another by-election coming up in Rochester and Strood.
"What we saw last night was the biggest and best night in UKIP's history
Video: 'UKIP Vote Risks Labour Government'
"We will now take the people's army of UKIP to the Rochester and Strood, and we will give that absolutely everything we have got."
Mr Farage earlier told Sky's Faisal Islam the strong UKIP result showed the Eurosceptic party was "ripping lumps out of the old Labour vote in the north of England".
Asked if he had a message for both Mr Cameron, who turned 48 yesterday, and Mr Miliband, he replied, "we're after you", adding: "Happy Birthday to David Cameron, and Ed Miliband, you have underestimated us."
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Gallery: UKIP Surge In By-Election Results
UKIP has its first elected MP after Douglas Carswell took almost 60% of the vote in the Clacton by-election.
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Mr Carswell won the seat with a majority of 12,404 over the Tory candidate Giles Watling.
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Liz McInnes won the seat for Labour in the Heywood and Middleton contest, but its majority of almost 6,000 in 2010 was slashed to just 617 votes.
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On a turnout of just 36%, Ms McInnes won with 11,633 votes, defeating UKIP's John Bickley on 11,016.
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Ed Miliband's party's majority had been almost 6,000 in 2010, but a UKIP surge saw a 17.65% swing to Nigel Farage's party.
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A triumphant Mr Carswell said "there is nothing that we cannot achieve" after winning Clacton.
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UKIP's first elected MP to Parliament forced the election after defecting from the Tories.
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Mr Carswell was the favourite to win, but there were still nerves on the night.
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Mr Carswell took almost 60% of the vote.
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Mr Farage said: "Congratulations Douglas Carswell, a brave and honourable man who has a just reward."
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Ms McInnes won with 11,633 votes in Heywood and Middleton, defeating Mr Bickley on 11,016.
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Despite UKIP's loss in the Lancashire constituency, Mr Bickley told Sky News "the Labour vote had collapsed".
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Mr Farage went on to tell Sky News: "We are ripping lumps out of the old Labour vote in the north of England. The truth of what has happened in the North today is that if you are anywhere north of Birmingham, if you vote Conservative you get Labour."
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He added: "And the reason we haven't won up there, despite a fantastic campaign, is that too many people have stuck with the Conservatives, not recognising that UKIP is now the challenger to Labour in every urban seat in the north of England."
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Turnout in Clacton was 51.2%, while in Heywood and Middleton it was just 36%.
Mr Cameron said UKIP's success in Clacton and better-than-expected showing in Heywood and Middleton both spoke to a "wider truth" that a vote for UKIP risked a Labour government.
"If you vote UKIP you are in danger of getting a Labour government with Ed Miliband as prime minister, Ed Balls as chancellor, and you'll get no action on immigration, no European referendum, and most importantly you won't get a continuation of the plan that's delivering success for our economy and security for our people," the Prime Minister said.
"That is the wider lesson of last night and we have several months to demonstrate that only a Conservative government can give people the stability and security that we all want to see."
Video: UKIP Finally Makes The Breakthrough
Mr Miliband, who would not be drawn on the nail-biting recount at Heywood and Middleton, said: "There won't be a shred of complacency from us as we reach out to all of those voters who didn't vote Labour and those who didn't vote at all."
He said the 2015 election was a "fight against disillusionment and despair about politics" which he was determined to win.
Mr Carswell, who triggered the Clacton by-election when he defected from the Tories, said UKIP's success revealed a "profound change in British politics".
Video: By-Election Highlights
Ms McInnes, who gained 11,633 votes in Heywood and Middleton where voter turnout fell to just 36%, said the by-election result was a win for the NHS.
Analysts said Labour's vote was damaged by the low turnout. Voter turnout was higher in Clacton, where 51.2% of voters cast their ballot.
Sky's Jon Craig said the dramatic decline of Labour's majority in Heywood would trigger further debate about Ed Miliband's leadership.
Video: Inside The UKIP Party's Party
Concerns over the result have been raised by some Labour MPs, with one branding the vote "awful" and "terrible" and a member of the shadow cabinet describing it as "very worrying".
Sky's Joey Jones said one senior MP had warned Monday's gathering of the Parliamentary Labour Party "could be an absolute bloodbath".
Voters in Heywood cast their ballot for a new MP following the death of Labour's Jim Dobbin last month, who held the seat from 1997 and was returned in 2010 with a significant majority.
Video: Interview: Labour MP
UKIP's next target is Rochester and Strood, where defector Mr Reckless is hoping to return to Parliament following his defection.
The by-election there is expected to take place early next month.
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