The former archbishop of Canterbury, Lord Carey, has accused David Cameron of making Christians feel marginalised.
He said it was a "bit rich" for the prime minister to tell religious leaders to oppose secularisation.
This follows comments made by the PM at a pre-Easter Downing Street reception for faith leaders.
A Downing Street spokesman rejected the criticism, saying Mr Cameron valued "the profound contribution" Christianity had made to UK life.
But Lord Carey wrote in the Daily Mail that the government seemed to be "aiding and abetting" aggressive secularisation.
He also said Mr Cameron had done more than any other recent political leader to increase Christian anxieties.
Many Christians doubted the sincerity of Mr Cameron's support of Christians' right to practise their faith, he said.
Lord Carey said: "I like David Cameron and believe he is genuinely sincere in his desire to make Britain a generous nation where we care for one another and where people of faith may exercise their beliefs fully.
"But it was a bit rich to hear that the prime minister has told religious leaders that they should 'stand up and oppose aggressive secularisation' when it seems that his government is aiding and abetting this aggression every step of the way.
"At his pre-Easter Downing Street reception for faith leaders, he said that he supported Christians' right to practise their faith. Yet many Christians doubt his sincerity."
Lord Carey also that said a recent ComRes poll suggested "more than two-thirds of Christians feel that they are part of a 'persecuted minority'".
"Their fears may be exaggerated because few in the UK are actually persecuted, but the prime minister has done more than any other recent political leader to feed these anxieties."
He said that Mr Cameron "seems to have forgotten in spite of his oft-repeated support for the right of Christians to wear the cross, that lawyers acting for the coalition argued only months ago in the Strasbourg court that those sacked for wearing a cross against their employer's wishes should simply get another job".
And Lord Carey spoke of being "very suspicious" that behind plans for gay marriage "there lurks an aggressive secularist and relativist approach towards an institution that has glued society".
"The danger I believe that the government is courting with its approach both to marriage and religious freedom is the alienation of a large minority of people who, only a few years ago, would have been considered pillars of society."
However, a Downing Street spokesman rejected the criticism, saying: "Christianity plays a vital part in the Big Society, from the many brilliant church schools to the huge number of charitable causes based in churches across the country.
"The prime minister values the profound contribution that Christianity has made and continues to make to the country, which is why he strongly backs it."
Desmond Swayne, a former Parliamentary aide to David Cameron, told BBC News that he was shocked to read Lord Carey's remarks.
"I was almost gobsmacked because I regard myself as a bible-believing Christian and my view is that the government couldn't have been more forthright in defending the interests and practices of Christians."
On the issue of gay marriage, Desmond Swayne said the government has done all it could "to take account of the objections of the Church of England and other churches which are against this development."
He added: "We've produced a package which maximises the freedom available to the churches - those that don't want to touch it, won't have to."
The National Secular Society, meanwhile, urged the prime minister to "ignore Lord Carey's theocratic and anti-democratic blustering".
"Nothing in the proposed same-sex marriage laws require Christians to conduct or partake in same-sex marriage, and Lord Carey has no right to insist that his discriminatory and intolerant views should prevail over those of the public and Parliament," executive director Keith Porteous Wood said.
Christians were "far from being marginalised in this country", he added.
He said the UK was "the only country in the world to give bishops the right to sit in its Parliament" despite "precipitously declining support, as shown by the congregations declining and ageing for many decades".