The Dean of St Paul's Cathedral has signed a letter to David Cameron urging the Prime Minister to axe work assessments for the disabled which can "cut short their lives".
The Very Rev Dr David Ison joined campaigners calling for the Government to address the "shameful offences" of its austerity programme.
In their letter they demand an end to the controversial work capability assessments (WCA) which "demean and distress" disabled people.
The missive, entitled The Downing Street Demand, claims Government policies force some of the most deprived members of society to "shoulder the heaviest burden of national debt created by the super-rich".
Addressed to the Prime Minister, the letter states: "In 2010 you said, 'I'm going to make sure no-one is left behind; that we protect the poorest and most vulnerable in our society'.
"The reality of the austerity programme is the opposite.
"Since your Government came to power, cuts have meant that disabled people are paying back nine times more than non-disabled people and those with the highest support needs are paying back nineteen times more."
Campaigners single out policies such as the WCA tests introduced in 2008 to assess entitlement to Employment and Support Allowance; the so-called bedroom tax and changes to benefits including the disability living allowance (DLA) and personal independence payment (PIP).
"The support needs of complex disabilities and mental health issues cannot be assessed by a tick-box system," the letter states. It suggests the WCA should be replaced with a "rigorous and safe system that does not cause unavoidable harm".
Dr Ison, who presided over Margaret Thatcher's funeral, met the campaign group 10,000 Cuts and Counting and members of the Occupy movement in London's Parliament Square to highlight the "human cost" of Government cuts.
"It's right to stand in solidarity with people from many different organisations to draw attention to the needs of some of the most deprived members of our society," Dr Ison said.
"Many disabled people feel desperate facing possible cuts in support, the bedroom tax, and in particular an inflexible and failing Work Capability Assessment scheme which can blight and even cut short their lives.
"The Government needs to respond by enabling disabled people to live with dignity and security."
Campaigners say some 56,000 people have signed a petition which calls for an immediate end to the "degrading" way the Government assesses need. They have called for tests to be provided by the NHS.
A Department for Work and Pensions spokesperson said: "It is important we don't simply write-off people who have a health condition or disability. The old incapacity benefits system condemned too many people to a life on benefits with little hope of moving back to work.
"Now people who can work will be given help to find a job while those who need unconditional support will get it.
"Through a series of independent reviews and by working with medical experts and charities, we have considerably improved the WCA process since 2010 to make it fairer and more accurate.
"The percentage of people entitled to Employment and Support Allowance is now at its highest level with over half of people completing a WCA eligible for the benefit."