Charlie Davis, 18, from Locks Heath, was among biology students left bewildered by the content of the exam paper.
More than 4,000 people from across the country have signed a protest petition.
But the Pearson group, which provides the Edexcel exams, said its papers ‘accurately reflect the curriculum’.
Students say the paper was a repeat of a previous paper for AS-level students two years ago and covered subject areas they were not taught.
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Charlie, who attends Itchen College in Southampton, said he initially thought he had been given the wrong paper.
He said: ‘I’m gutted. The two biology papers, especially the first one, was probably the worst paper I have ever taken in my time in education.
‘I’m not wanting to use it as an excuse, but everyone else felt the same.
‘I don’t even know what they were thinking when they thought of the questions.’
He added: ‘We hope the exam board will consider lowering the grade boundaries significantly so it’s easier to get higher grades.’
Charlie’s mum Claire Blacknell added: ‘Someone needs to investigate why this has happened. I’ve never felt so incensed and upset to see my son be so despondent after working so hard for this exam.’
A statement from Pearson said: ‘Our exam papers accurately reflect the curriculum that schools, teachers and learners have been working towards.
‘In the case of the unit 4 biology paper the specification is clear that some content may be drawn on AS material.’