Academic staff at the Open University have passed a vote of no confidence in their vice-chancellor, Peter Horrocks.
Members of the University and College Union are now calling on Mr Horrocks to resign "as soon as possible".
Mr Horrocks had angered staff by saying academics "get away with not teaching" and that impending cuts were "reprioritising".
He later apologised by letter, saying: "I sincerely regret that my careless language caused offence or hurt."
He went on: "I would like to meet with as many of you as possible in coming weeks, so you can express your concerns and so I can address any misconceptions that some of you believe I have about your teaching."
The row comes as the OU is planning a "radical overhaul" of the nearly 50-year-old institution, which aims to save £100m from an annual budget of £420m.
The OU, which is projecting an annual deficit of around £20m and has been badly affected by a collapse in the number of part-time students in England, says half of the money saved will be reinvested into the institution.
Mr Horrocks said the changes would result in "a revitalised and redesigned OU".
But now at a UCU branch meeting, members have passed a motion saying: "This general meeting has no confidence in our current vice-chancellor, or in his plans and intentions for the future of our university.
"On the basis of recent events, he has shown that he does not understand the university's teaching model, nor the importance of the OU's research base.
"We believe the best way of avoiding damage to the public image of the OU is for the VC to step down as soon as possible. We therefore call upon the VC to resign."
A spokesman for the OU said: "We are midway through an ambitious programme to transform the way we teach and support our students so that they have the best preparation for the challenges of a rapidly changing world.
"The plans have sparked a lively internal debate as well as a degree of concern.
"We can confirm that these concerns will be discussed more thoroughly at a special meeting of the University Council and later at the OU's academic governing body, the Senate."
Who is Mr Horrocks?
Mr Horrocks had previously worked at the BBC for 33 years, leaving his post as director of the BBC World Service Group in 2014.
He took up the post at the OU three years ago in 2015.
The OU was founded in 1969 to offer higher education distance learning to students who often did not fit the traditional undergraduate mould - many were older and studying part-time while working.