Lecturers, lab assistants and librarians will stop work at Sydney University for the next two days over better pay and conditions.
The 48-hour industrial action means classes won't be taught and research won't be conducted as frustrated staff negotiate with university management over a new enterprise agreement.
National Tertiary Education Union representative Dr Nick Riemer said the picket line was a necessary escalation.
"Our members are just incensed. It's not acceptable that they're being pushed to the limit," he told AAP.
"Management at the university is broken with very overpaid senior executives who don't know the nature of our work."
He expects hundreds of staff to participate starting from 7am, demanding a wage increase of 15 per cent over the next two years.
Other pressing demands include protection of academics' right to a 40 per cent research component of their workload and controls on a ballooning workload.
"Staff feel completely punished for doing their jobs and they're at the end of their tether," the linguist said.
Sydney University posted a statement on Tuesday advising students that they can still come to campus.
It boasted that it had "some of the best wages and conditions of any university in Australia".
But Dr Riemer countered that did not mean much to casuals, who work from semester to semester without a fixed income, as well as overworked staff.
"The university shouldn't be run like a business, but as a democratic institution for the public good".