Shadow work and pensions minister Margaret Greenwood said the proposals make no sense, as the Government prepares to expand its flagship Universal Credit benefit.
Work and Pensions Secretary David Gauke rejected the claims, saying most benefits are now claimed online and the move makes sense financially.
Asking an urgent question on the issue in the Commons, Ms Greenwood said: "The impact of the closures will undoubtedly be felt by the poorest and most vulnerable in our society.
"By closing such a large proportion of the DWP estate, the Government will be forcing claimants to travel further to access the vital services that they need, so impacting on the lives of sick, disabled people, carers and parents with young children."
Ms Greenwood challenged Mr Gauke to publish an equality analysis for each site to assess the impact of its closure.
She added: "The Government plans to subject an additional one million claimants to in-work conditionality, a process under Universal Credit by which people in work may be required to attend jobcentres.
"What assessment has the minister made of the impact on demand for jobcentre services as a result of increased in-work conditionality?
"The decision to close jobcentres on this scale at the same time as accelerating the rollout of universal credit full digital service makes no sense."
Mr Gauke said the changes would save £140 million a year for the next 10 years.
"Eight out of 10 claims for Jobseeker's Allowance and 99% of applications for Universal Credit full service are now made online," said Mr Gauke.
"This means that DWP buildings are used much less, with 20% of the estate currently underutilised.
"Our estate plans must reflect the way customers interact with DWP now and in the future - not how they behaved in the past."
While around 750 jobs have been put at risk by the closures, Mr Gauke said "these changes will not lead to a reduction to the number of frontline jobcentre staff".
He added: "This is taxpayers' money that we are talking about and what we can do is we can find savings in DWP's estate budget and at the same time provide modern, up-to-date jobcentres that provide the service that is needed.
"I think it is right and I am disappointed that if the party opposite are going to be standing against the careful and sensible use of public money, which is exactly what we are delivering."
A PFI contract for the DWP estate is due to expire in March, Mr Gauke said.