The call comes amid repeated accusations that league tables are forcing schools to concentrate on the best-performing pupils and to ignore the one in 12 who leave with no qualifications.
This week half a million pupils received their results, which again showed record numbers of examination entries and passes.
But David Hart, general secretary of the National Association of Head Teachers, said that the exam system is hindering weaker pupils.
"The current system, tied to league tables, is producing a concentration on those capable of achieving the five or more A-C grades, and is causing real problems for the lower achievers - although, as a country, we have recognised that we need to take urgent and effective action to help these people," he said.
"The GCSE also militates against the idea of a coherent 14 to 19 curriculum. The NAHT has long doubted the value of GCSE as an exam at 16-plus, particularly with the introduction of the national curriculum and major reforms taking place at 17-plus and 18.
"We need some sort of exam, but we need one which produces results of real benefit to students, employers, further and higher education."
His criticisms were backed by the Association of Teachers and Lecturers. "An exam as important as this should be subject to regular scrutiny," said a spokesman. "The GCSE has increasingly become a narrow search for the successes and failures, the sheep and goats."
John Dunford, president of the Secondary Heads Association, said: "In the long term, a sensible 14 to 18 system of qualifications would not have a major national exam at 16. But things cannot be changed overnight. The GCSE has been a tremendous success story and it should only be dispensed with when we have something better to put in its place."
This year saw a 1.1 per cent increase in the total number of entries, with a new high of 5,711,558 exams taken by roughly 500,000 students. The proportion achieving the top grades of A-C rose by 1 per cent, following the pattern of previous years.