Hundreds of staff at the Driver and Vehicle Licensing Agency (DVLA) will launch a four-day strike on Tuesday in a dispute over Covid-related safety.
Members of the Public and Commercial Services union (PCS) at the site in Swansea, South Wales, will walk out until Friday after talks failed to resolve the row.
The union said those involved will include operational staff who have not been working from home.
Further industrial action is threatened if managers do not make the safety improvements the union is demanding, such as reducing the number of staff working at the site.
There was an outbreak of Covid at the offices last year but the DVLA said it has followed official health guidance for keeping staff safe.
The agency said the strikes were likely to delay paper applications it receives as well as calls to its contact centre, but online services will still be available.
The PCS said progress had been made in talks, but it added that the lack of immediate moves to reduce numbers on site means the industrial action will go ahead.
Agreement had been reached on removing more than 300 desks, revising risk assessments which has led to a further 300 staff being sent home, and a commitment on how to proceed in talks over the coming months.
PCS general secretary Mark Serwotka said: “That PCS members are prepared to take unprecedented strike action shows just how badly DVLA management have failed in their responsibility to keep staff safe.
“No civil servant should have to go on strike to guarantee their safety at work.
“It is inconceivable that this Government is allowing DLVA to risk the lives of its staff by forcing them into a workplace that is so clearly not safe.
“We call on the DVLA and Transport Secretary Grant Shapps to enter into meaningful negotiations with the union, as we are determined to only send our members back into DVLA when the workplace is safe again.”
A DVLA spokesman said: “The safety of our staff is paramount, and we have continuously adapted our measures over the past year and will continue to do so.
“There is currently not a single member of staff in the 10-day isolation period, out of a workforce of more than 6,000.
“DVLA has ensured that it has followed Welsh Government guidance at every single point throughout the pandemic having consistently worked with Public Health Wales, environmental health and Swansea Bay Health Board to introduce a wide range of safety measures.
“This has enabled DVLA to continue to deliver essential services right across the UK in a Covid-secure way.”