Around 600,000 people could lose Disability Living Allowance (DLA) - described as "outdated" by ministers - when it is replaced by the new Personal Independence Payment (PIP) on Monday.
The total number of people claiming DLA was 3.2 million last year - a drastic increase from 1.1 million when it was introduced in 1992. The new PIP has tighter controls and a face-to-face assessment for claimants.
Studies by the Department for Work and Pensions (DWP) estimate that the disability changes alone could save around £2.2billion and lead to 600,000 fewer claimants by 2018.
Campaign groups say disabled people could lose between £20.55 and £131.50 under the new system, which begins for new claimants in parts of the north of England, before being introduced for all new claimants in the rest of the country from June.
The new row will prolong a bitter political battle over the raft of benefit changes introduced this month.
George Osborne, the Chancellor, provoked Labour ire after linking the case of Mick Philpott, who killed six of his children in a house fire in Derby, with the wider benefits culture.
DLA currently comes in two parts - a "core" payment of up to £77.45 a week and a "mobility component" worth up to £54.05. Ministers argue it is overdue for reform and does not reflect medical opinion on dealing with disability.
Esther McVey, minister for disabled people, said: "Disability Living Allowance is an outdated benefit introduced over twenty years ago and needs reform to better reflect today's understanding of disability.
"At the moment the vast majority of claimants get the benefit for life without any systematic re-assessments and around 50 per cent of decisions are made on the basis of the claim form alone - without any additional corroborating medical evidence.
"The Personal Independence Payment will include a new face-to-face assessment and regular reviews - something missing in the current system. This will ensure the billions we spend give more targeted support to those who need it most."
Richard Hawkes, chief executive of disability charity Scope said: "It is cutting a financial life-line for disabled people, which helps them meet the extra costs of day-to-day living when you have a disability. The reform is fundamentally flawed.
"It doesn't help that ministers are able to predict exactly how many disabled people will receive support before they have even been tested. This raises alarming questions that the Government is working to arbitrary targets."
Meanwhile, unpublished new research has shown that public attitudes towards the welfare state are currently more negative than they have been for generations.
A study of the public's views on benefits for the Joseph Rowntree Foundation - produced by Ipsos MORI, the pollster, and Demos, the think tank, and going back over 30 years of surveys - has show that dissatisfaction with the system has grown among voters of all ages, particularly the elderly.
In 1983, the year of Margaret Thatcher's landslide general election victory for the Conservatives, nearly half of all voters (46 per cent) agreed that "benefits are too low and cause hardship", with a similar percentage agreeing in 1997. In 2011 this had fallen to 19 per cent.
In 1987 55 per cent of voters thought more should be spent on welfare for the poor even it meant taxes going up. This fell to 44 per cent in 1997 but was down to just 28 per cent in 2011.
Asked in 1987 whether they agreed that many people who got social security did not deserve any help, 31 per cent agreed, rising to 33 per cent in 1997 and 35 per cent in 2011.
There was a sharper rise in those agreeing that if welfare benefits were not so generous, people would learn to stand on their own two feet.
Some 33 per cent agreed with this in 1987 and 40 per cent agreed in 1997. By 2011 the figure had increased to more than half, 54 per cent.
Bobby Duffy, the managing director of Ipsos MORI, said: "It is undoubtedly the case that views of the welfare system and recipients have hardened over the last few years - but this analysis also makes clear that there has been a generational shift.
"Younger generations don't have anything like the connection to the welfare state that previous generations have, and that's a real challenge for the future.