Fringe player UKIP, ridiculed until Thursday as an assembly of clowns and political lightweights, trounced Cameron's Tories from local councils and appeared to make coalition partner Liberal Democrats appear irrelevant as it captured a third place in local politics.
UKIP has yet to enter Westminster Parliament but leader Nigel Farage declared the results were a game-changer and would transform British politics.
UKIP is widely expected to capture a parliamentary seat if there's a by-election due to death or resignation of an incumbent member of the House of Commons.
UKIP's agenda suggests its win presages a further tilt to the right in British politics that the struggling coalition of Cameron's Conservatives and Liberal Democrat leader and Deputy Prime Minister Nick Clegg would need to follow in order to stay ahead of advancing UKIP.
Cameron said he would "work really hard to win back" supporters who decided to vote for UKIP instead of Tory local councilors.
UKIP wants a tougher stand on Europe, immigration freeze, wider policing and more jails and a crackdown on welfare state abuse. It denies it's a racist party despite its clear right-wing agenda and has introduced reforms analysts see as populist, aimed to wean away left-wing Labor Party supporters.
UKIP won more than 140 seats and averaged 25 percent of the vote in the wards where it fielded candidates.
The Conservatives lost control of 10 councils, but retained 18, while Labor gained two councils and boosted its councilors by nearly 300, BBC election data indicated.
The elections took place in 27 English counties and seven unitary authorities, as well as on the island of Anglesey, northwest of Wales. About 2,300 council seats were contested throughout England, seen as a major mid-term test for the coalition.
The BBC's projected national share of the vote put the opposition Labor Party in the lead with 29 percent of the vote and the Conservatives in second place with 25 percent, UKIP in third place with 23 percent of votes. The Conservatives' coalition partners Liberal Democrats trailed with 14 percent of the vote.
UKIP, which held a handful of local council seats going into the election, had the biggest advance of any fourth party since World War II, the Guardian said.
"We've been abused by everybody, attacked by the entire establishment who did their best to stop ordinary decent people from going out and voting UKIP, and they have done in big, big numbers," Farage said. "At the end of today we are going to have a fair tally and it sends a shockwave through the establishment."
Cameron said, "We need to show respect for people who have taken the choice to support this party and we are going to work really hard to win them back."
Farage told the BBC the party had taken its "first substantial step toward a party that can credibly win seats at Westminster."
"It's a fascinating day for British politics. Something has changed here," he said.
"I know that everyone would like to say that it's just a little short-term, stamp your feet protest -- it isn't. There's something really fundamental that has happened here.
"People have had enough of three main parties, who increasingly resemble each other. The differences between them are very narrow and they don't even speak the same language that ordinary folk out there, who are struggling with housing and jobs, speak."
Clegg told the Guardian in an interview the struggle on the right of British politics caused by UKIP's surge was pulling Cameron away from the center ground and making day-to-day progress in the coalition more difficult.
Clegg vowed to "dig in my heels and make sure the center of gravity of the government as a whole does not get pulled rightwards due to the internal dynamics of the Conservative Party."