Speaking to ITV News on Monday, the Tory minister without portfolio raised concerns that the defeat at the hands of Nigel Farage's eurosceptic party at the Eastleigh by-election would encourage the prime minister to abandon his modernising agenda.
"If you imitate Ukip you make them look relevant, then you drive moderate people to vote Lib Dem. I cant think of a more certain way to lose the general election than with a lurch to the right," he said.
Clarke, who is often described as the sixth Lib Dem member of the cabinet due to his liberal-conservative values, was replaced as justice secretary by the more right-wing Chris Grayling in September.
In the wake of the Tories dismal third place finish in last week's by-election, many in the party have urged Cameron to focus on shoring up the core Conservative vote.
Clarke also yesterday rubbished Grayling's suggestion a future Tory government would withdraw Britain from the European Court of Human Rights, arguing it is necessary to protect people from a "tabloid lynch mob".
He said: "In today's highly tempestuous, tabloid newspaper-dominated world, with a lynch mob every week for somebody or other, you need a convention on human rights, you need to be able to apply it, particularly, unfortunately, when unpopular individuals being campaigned against in the newspapers are being pursued by officials or somebody. That's what the convention of human rights is for."