Much of the party's operations will be transferred to the north east of England where Labour already has a call centre in North Shields.
The move will see New Labour vacating the building whose name has become synonymous with its "control freakery" and the vigorous central command it sought to impose on the party across the country.
Phrases like the "Millbank tendency", coined by left-wingers to deliberately echo the name of the Trostkyite Militant Tendency group which infiltrated the party in the 1980s, have become part of the political vocabulary.
Millbank-based officials, led by party general secretary Margaret McDonagh, played a key role in the controversial selections for the Labour candidates for London mayor and leader of the Welsh Assembly.
In both selections the choice of party members - Ken Livingstone and Rhodri Morgan respectively - were blocked in favour of candidates approved by Prime Minister Tony Blair.
Both impositions ultimately backfired. Alun Michael, Mr Blair's choice in Wales, was forced to resign. Frank Dobson, his choice for London, was humiliated at the polls when Mr Livingstone ran for mayor anyway as an independent.
Long way from Walworth Road
Labour moved its headquarters to Millbank, which is situated just down the road from the House of Commons, ahead of the 1997 election.
At the time there was much anger among traditionalists that the old headquarters in trade union-owned Walworth Road was being abandoned.
The former HQ had been named John Smith House after the tragic death of the Labour leader.
It is expected that the press, policy and general secretary's office will remain in London while other functions, such as distribution and printing, election staff, local government and conference organisation, will move elsewhere.
Redundancy concerns
Union sources said the lease on Millbank was coming to an end and Labour wished to move to cheaper premises.
A GMB union spokesman said: "Workers have given loyal service to the Labour Party over many years throughout some of the party's most traumatic times.
"We expect them to be treated properly now.
"Redundancy and relocation terms are high on our lists of concerns."