The University of Salford is to axe about 200 posts.
It said that most of the positions would be shed from administrative areas and were part of a "strategy to enhance and improve" the university.
Discussions are underway with union representatives to try to avoid compulsory redundancies.
The university said part of the plans would see the creation of new posts and that attempts would be made to redeploy staff.
A University of Salford spokeswoman said: "As part of our strategy to enhance and improve our teaching and student experience, we are embarking on a programme to deliver more effective administrative and professional services.
"This will affect around 200 employees but a significant number of new roles are being created which will be filled by affected staff.
"The number of job losses is expected to be significantly lower than the affected figure.
"We remain fully committed to working with the unions and staff to avoid compulsory redundancy where possible."