About 40 University and College Union employees are to leave this summer under a voluntary redundancy scheme.
The departures, which will be completed by the end of August, are expected to cost the union about £1 million.
The scheme was set up earlier this year as part of restructuring proposals drawn up by Sally Hunt, the general secretary, after the 2006 creation of the UCU through the merger of the Association of University Teachers and the lecturers' union Natfhe.
Ms Hunt's original restructuring plans were rejected by the trade unions representing UCU staff, and a new structure was finally agreed more closely mirroring existing structures and envisaging most employees keeping their positions, grades and salaries.
But the original voluntary severance scheme was not withdrawn, and many long-serving staff, mostly former Natfhe employees, decided to leave.
In a report on a meeting with Ms Hunt in June, Amicus, the UCU staff representative union, said: "We haven't yet had any real discussions about how to ensure that service to members isn't compromised by the large number of people leaving."
Amicus also predicted that the voluntary scheme would result in a "worrying reduction" in the number of black staff employed by the union. An impact assessment of the new structure would also show "a serious reduction in the number of women in senior posts", it added.
The 40 departures represent about 20 per cent of the union's 200 or so staff. Those leaving include London regional official Jenny Golden; head of communications and public affairs Paula Lanning; HR director Annette Dalchow and her deputy Trudy Mackie.
A UCU spokesman said the union never commented on internal staff matters.