At least 143 secondary schools are at risk of being labelled as failing after they were affected by the GCSE English grading fiasco.
Schools could be forced to turn into academies and headteachers' jobs jeopardised if they fall below the government's GCSE floor target in the wake of the crisis, the Association of School and College Leaders said.
The warning came as Ofqual chief Glenys Stacey admitted that she would have forced one of England's biggest exam boards to alter its GCSE English boundaries to avoid grade inflation.
The regulator has the power to direct grade boundary changes and would have done so if Edexcel had not revised them, she told the Commons education select committee.
As Ms Stacey gave her evidence, ASCL raised concerns about the numbers of schools which have seen their overall GCSE results drop due to the English grading crisis.
This year, secondary schools in England will be judged as under-performing if less than 40% of pupils get at least five Cs, including English and maths, and if students are making below national average levels of progress.
Those that fail to meet the target face being taken over and turned into an academy, the Press Association reported.
ASCL said on Tuesday that 143 schools had told them that their results had left them below the benchmark when they had expected to be above it.
In total, 730 schools had responded to the poll, with 641 saying that their results had been lower than expected this year. Of these, around 500 had said the main reason for this was GCSE English.
ASCL general secretary Brian Lightman said the grading fiasco "could cause enormous reputational damage to these schools, and even cost school leaders and teachers in these schools their jobs, which would be a gross injustice in view of the way these results have come out."
He added: "These are schools that have been improving and doing all kinds of things to raise standards, and they now find themselves in a completely unexpected position."
Mr Lightman said that the union had been in talks with the Department for Education and Ofsted about the issue.
"If any of our members are challenged on the basis of results like this, which we think are unfair, we will do everything we can to defend them."
Leaked letters published today showed that Ofqual pressurised Edexcel to alter its GCSE English grade boundaries just two weeks before results were published last month.
Appearing before the Commons education select committee, Ms Stacey was asked what Ofqual would have done if Edexcel had stuck to its first response to the regulator, and insisted that its proposed grade boundaries were fair.
"If they had done so, then the legislation provides that the regulator can direct grade boundary changes," Ms Stacey said.
Pushed on whether Ofqual would have done this, she added: "I think we would have done, yes."
The leaked correspondence, seen by the Times Educational Supplement (TES) show that Ofqual wrote to Edexcel on August 7 amid concerns that there would be a rise in C grades, calling on them to act quickly to produce results that were closer to predictions for the subject.
The board responded a day later, saying it believed its proposed grade awards were "fair" and there was no justification for further changes.
It added that if Ofqual still wanted an alteration, that the board could move the minimum requirement for a C grade for one of the English units up to 65 marks out of 96 - 10 marks higher than in January when it stood at 55.
Ofqual replied on 9 August, with a letter from standards director Mr Dennis Opposs that stated Edexcel is obliged to ensure its results are consistent with other awarding bodies, whose results were close enough to predictions.
Alex Cunningham, Labour MP for Stockton North, asked Ms Stacey why Edexcel had changed its mind, saying "was it the fact that you adopted a strong-arm tactic to tell them 'you must ensure that these grades are downgraded'?"
Ms Stacey replied: "What changed was, that we knew, looking at that, that there would be a six or seven per cent increase, grade inflation, that we did not think to be right or justifiable.
"We therefore wrote to Edexcel pointing out that they needed to bring the qualification in appropriately. They reflected on that and it's quite right and proper that they should have done."
She also told MPs Ofqual had also written to the WJEC exam board.
Amanda Spielman, who chairs Ofqual, told the committee she was surprised how high the grade predictions were at some schools.
"You might have thought that this year, in the first year of a completely different exam, schools would be a bit more cautious about their predictions and have brought them down a bit," she said.
"I'm not saying it is the schools' fault, I'm saying school expectations were in a very different place. We would have expected in the face of a new specification to see schools being more cautious and what we actually saw was that school expectations for Cs went up by 2%."
In a written submission to MPs ahead of Tuesday's evidence session, Ofqual also said that nobody could have seen that January's results were too generous, and that all the evidence pointed towards decisions being harsh.
And it insisted that there has been no political interference in the exams.
The select committee will take evidence from education secretary Michael Gove on Wednesday.
An Edexcel spokeswoman said at the time the leaked letters were issued, other exams boards had already made decisions over their grade boundaries, and had them accepted by Ofqual.
"We felt that the original grade boundary changes suggested by Ofqual, based on prediction data and the decisions of other awarding organisations, would not enable us to adequately reflect student work in their grades.
"After extensive discussion with Ofqual, we agreed a June grade boundary which took account of our concerns to recognise the candidate performance our examiners observed. This reported results slightly above original Ofqual predictions.
"We are therefore satisfied that the final grade boundary we set for June enabled us to fairly reward learners as well as uphold the standard of the GCSE."