Staff at 74 universities across the UK are beginning a 14-day strike over pensions, pay and conditions.
The University and College Union is holding strikes between 20 February and 13 March and has estimated more than a million students will be affected.
The union described this latest strike as "solid". It follows eight days of action in November and December.
Action also took place in February and March 2018, meaning some students face disruption for the third time.
The universities say strikes are not the way forward and have promised to do all they can to minimise the impact of industrial action on students.
The UCU says 50,000 of its members will take the action over workloads, pay, a 15% gender pay gap, a black and minority ethnic pay gap, increased casualisation and changes to pensions for staff in the Universities Superannuation Scheme (USS).
The union is angry members are now having to pay 9.6% in pension contributions, up from 8%, and wants universities to pay the full increase instead.
In addition to striking, union members are taking other forms of industrial action, including working strictly to contract, not covering for absent colleagues and refusing to reschedule lectures lost during the strikes.
217,065academic staff were employed in 2018/19
72,750 or 34%of lecturers were employed on short-term contracts
29,150 or 13% were paid by the hour
4,240were on a zero hours contract
General secretary Jo Grady said: "This unprecedented level of action shows just how angry staff are at their universities' refusal to negotiate properly with us."
But the Universities and Colleges Employers Association (UCEA) says it has invited the union to further talks and is "dismayed" by "damaging strike action".
University of Southampton president and vice-chancellor Prof Mark Smith, who chairs the UCEA, said: "We are very sorry for the impact industrial action has on students' study.
The association says employers have increased their pension contributions from 18% to 21.1% of salary, paying in an extra £250m each year.
Oxford Brookes University vice-chancellor Prof Alistair Fitt, a member of the Employers Pensions Forum for Higher Education, said universities were doing all they could to lessen the impact on students and many had opened telephone support numbers, special web pages and strike helpdesks.
An online survey, published by The Student Room earlier this week, suggests 47% of students think it is right for lecturers to strike.
And many students affected by the strike last term told BBC News they understood why lecturers' were taking action, even though they were missing out.
But many students are angry they are losing out on lectures and tutorials in the run-up to exams.
Sarah Howlett, a final-year English student at Exeter University, told BBC News the strike was "a bit of a setback", not least because her dissertation was due in in April.
"It's the feeling that if I encountered a problem or needed feedback, I can't get that - it would be nice to pop round to their office or send an email but I won't be able to do that," she said.
"I do sympathise with why they're striking but it feels like they've done quite a few strikes and that there could be a less disruptive and more effective way to get their desired outcome."
Her friend Emma Crawford, a third-year geography student, said she was anxious because her final-year dissertation was due in in March.
"I understand why they're striking but the time they're doing it is a critical time for me," she said.
"I'm angry that we've paid over £9,000 a year and we're missing lectures and contact time - to me, it's a waste of money."
Students at a number of universities, including York, Newcastle and Sheffield Hallam, have started petitions asking for money back from their universities because of the loss of contact hours.
The Sheffield Hallam petition has about 14,000 signatures and is asking for £863.33 reimbursement per affected student for 14 days of disruption, based on the amount of fees paid.
Third-year student Tom Barton, who set up the petition, told BBC News he felt frustrated by the strikes last term.
"I missed out on a lot of tuition in a crucial period and it definitely affected my grade for some modules," he said.
"So when we found out they were doing another strike which would be even longer, we felt like we had to do something to get our voices heard, because no-one has ever listened in the past."
However, Tom said, he was supportive of the lecturers' action.
"We definitely support the strike, that's something that I have tried to make as clear as possible throughout all of this," he said.
"We stand with our lecturers on this. However, we shouldn't be disadvantaged."
Francis Clarke, of Birmingham University, said he and colleagues were not "relishing the prospect of having to take more strike action" but the overall mood was one of "determination and defiance".
"Nobody takes strike action lightly - after all, it takes us away doing the jobs we are proud to do and it means we won't get paid for up to 14 days," he said.
"Sadly, though, these problems have been building for years and despite the best efforts of our local [UCU] branch, as well as national UCU negotiators, university employers have consistently failed to address these serious concerns."
He and his colleagues did understand students' concerns and were "disappointed that we are in this position", he added.
What do the official statistics show?
Statistics from the Higher Education Statistics Agency (Hesa) show there were 217,065 academic staff working in UK universities in 2018-19.
- 72,750 (34%) were on fixed-term contracts.
- 29,150 were paid by the hour
- 4,240 were on zero-hours contracts
Universities also employed 222,885 non-academic staff in 2018-19, such as managers, student welfare workers, secretaries, caretakers and cleaners.
When is the action?
The UCU has set out 14 days of action over a period of four weeks:
- Week one: Thursday 20 and Friday 21 February
- Week two: Monday 24, Tuesday 25 and Wednesday 26 February
- Week three: Monday 2, Tuesday 3, Wednesday 4 and Thursday 5 March
- Week four: Monday 9, Tuesday 10, Wednesday 11, Thursday 12 and Friday 13 March
Which universities are affected?
A total of 47 universities have staff taking part in action over both pensions and pay and conditions:
- Aston University
- Bangor University
- Cardiff University
- University of Durham
- Heriot-Watt University
- Loughborough University
- Newcastle University
- Open University
- University of Bath
- University of Dundee
- University of Leeds
- University of Manchester
- University of Sheffield
- University of Nottingham
- University of Stirling
- University College London
- University of Birmingham
- University of Bradford
- University of Bristol
- University of Cambridge
- University of Edinburgh
- University of Exeter
- University of Essex
- University of Glasgow
- University of Lancaster
- University of Leicester
- City University
- Goldsmiths College
- Queen Mary University of London
- Royal Holloway
- University of Reading
- University of Southampton
- University of St Andrews
- Courtauld Institute of Art
- University of Strathclyde
- University of Wales
- University of Warwick
- University of York
- University of Liverpool
- University of Sussex
- University of Aberdeen
- University of Ulster
- Queen's University Belfast
- Birkbeck College, University of London
- Soas, University of London
- University of Oxford
- University of East Anglia
Staff at 22 universities are taking action over pay and conditions:
- Bishop Grosseteste University
- Bournemouth University
- Edge Hill University
- Glasgow Caledonian University
- Glasgow School of Art
- Liverpool Hope University
- Liverpool Institute of Performing Arts
- Queen Margaret University, Edinburgh
- St Mary's University College, Belfast
- Roehampton University
- Sheffield Hallam University
- University of Brighton
- University of Kent
- Bath Spa University
- Royal College of Art
- University of Huddersfield
- University of Winchester
- University of East London
- Leeds Trinity University
- UAL University of the Arts London
- De Montfort University
- University of Greenwich
Staff at five institutions are taking action over pensions only:
- Scottish Association of Marine Science
- Institute for Development Studies
- Keele University
- King's College London
- Imperial College London