The NSPCC will close its 150 local service centres and open 40 larger regional centres over the next three years.
The move will mean many of the charity's 800 child protection staff will have to change locations if they want to retain their jobs.
An NSPCC spokesman denied that the move, which will concentrate the organisation's work in areas of urban deprivation, would result in an overall reduction in the charity's workforce.
But he added: "We recognise that if we are going to move buildings, some of the workers may not want to go that way."
The move is part of the charity's seven-year strategy being put in place by chief executive Andrew Flanagan, who joined last year.
The strategy will focus the charity's work on seven priority areas: neglect; physical abuse in high-risk families; sexual abuse; children under one year old; children with disabilities; children from certain black and minority ethnic communities; and looked-after children.
Some buildings will close when their leases expire, and some in larger population areas will be upgraded to accommodate more staff.
The NSPCC shed 45 jobs at nine local service centres last year because their work did not fit into the new strategy. But it predicts its workforce of about 2,000 will increase by 300 by 2016.
"This is not a cost-cutting exercise," the spokesman said. "We are reshaping over a period of time."