The Conservatives are trying to push up to 10 million voters off the electoral register to "make it easier for themselves to win the election," Harriet Harman has said.
Ms Harman says research by the independent Electoral Commission found most of those who will become ineligible to vote are likely to have been Labour voters.
The Labour deputy leader told Sky News she was "shocked" by the Government's "unbelievable" attempt to change the rules.
Coalition plans would require each individual to sign up, ending the system where one person can register their household.
"The people who as a result of these rule changes are most likely to be pushed off the register are young people, people living in rented accommodation rather than people who own their own home, and people who live in cities rather than rural areas," she said.
"They are people who obviously the Tories think are less likely to vote Tory, so they're making these changes and they're going to be pushed off the register."
She described the right to vote as "absolutely fundamental in a democracy".
Ms Harman will use her closing speech at Labour's conference in Liverpool to criticise the policy.
She will say the Electoral Commission expects the number of eligible voters who are registered to drop from 90% to as low as 60%.
The people who are bumped off the list are likely to be "predominantly poor, young or black, and more liable to vote Labour," she will tell delegates.
She will accuse the Liberal Democrats of "colluding" with the Conservatives on the issue "to their eternal shame".
Ms Harman also told Sky News the party's conference had been overshadowed by the grim news of job losses at BAE Systems.
Describing it as a "terrible situation" and warned the Government must not be "complacent" about the problems facing the global economy and the rise in youth unemployment.