A report, carried out by Sheffield Hallam University, said Doncaster will lose around £410 per working adult by the 2020/2021 tax year.
This means Doncaster is set to lose more than the Yorkshire average of £360. The region is one of the hardest hit outside London.
The research team, which includes Oxfam and the Joseph Rowntree Foundation, looked at welfare reforms that have been announced since the 2015 general election and that will be implemented in stages from April this year.
These include reduced tax credits, especially for larger families; limiting housing benefit in the social sector to the private-rented rate; restricted entitlement to housing benefit for 18 to 21 year olds and the extension of the benefit cap.
Blackburn, Blackpool and Bradford are also among the worst hit, while areas in the south such as Richmond upon Thames and South Buckinghamshire have not felt the same pinch.
The report estimates that couples with two or more dependent children will lose an average of £1,450 a year, while lone parents with two or more children lose an average of £1,750 a year.
Nigel Ball, Labour councillor for Conisbrough ward said: “This government seems committed to hitting the most vulnerable people in our society including here in Doncaster.
“Millionaires are walking around with tax breaks while people at the bottom are getting money taken off them. It’s shocking and appalling.”
Doncaster Central MP, Dame Rosie Winterton, hit out at the government’s changes to welfare.
She said: “George Osborne wanted us to believe that he had reversed his plan to cut tax credits, but as with so many of his promises, the substance doesn’t match the spin.
“The cuts are going ahead, and, as this report shows, it will affect hundreds of low-paid working families here in Doncaster – particularly those who are in insecure jobs such as zero hours contracts or who take on more work to help pay the bills.”
A government spokesman said: “The government is determined to deliver a new settlement for the British people, one that will create a higher wage, lower tax and lower welfare economy. Our welfare reforms ensure that the system is fair both for those who need it and the taxpayers who fund it.”