Up to 200,000 of those who will be affected receive Disability Living Allowance and around 100,000 live in homes specially adapted for their needs.
The National Housing Federation is calling on ministers to rethink their plans.
Under the proposals, some 670,000 social housing tenants across Great Britain will lose an average of £676 per year because their homes will be deemed too large for their needs. As a result of the proposed cuts to housing benefit many tenants will end up going into debt and others will be compelled to move.
By including disabled people in the measure, the Government is going back on earlier commitments to protect their homes and financial security, the NHF said.
There is a precedent for protecting disabled people from measures in the Welfare Reform Bill. The Department for Work and Pensions has already agreed to exempt recipients of the Disability Living Allowance from the household benefit cap, on the grounds that they are "likely to have less ability to adapt to a reduction in their benefit".
The NHF is calling for the same principle to be applied to benefit reductions arising from the new measure against those deemed to be under-occupying their social home.
NHF chief executive David Orr said: "The cuts to housing benefit for households deemed by the Government to be under-occupying are extremely harsh and could effectively compel thousands of people to lose their homes. Of course, under-occupation in the social housing sector should be tackled. But slashing people’s housing benefit and pushing them into poverty is not the answer.
"At the very least, the Government must keep its pledge to protect the most vulnerable and exempt them from this unfair cut for all recipients of Disability Living Allowance and all disabled people living in specially designed or adapted properties. Failure to do so will raise serious questions about its commitment to help those who need help most."
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