Delivering the annual OCR KPMG education lecture at the Royal Society of Arts, in London, he offered a list of reasons why half of all 16-year-olds fail to get five good GCSEs.
Mr Tomlinson said certain key groups, including white boys from deprived backgrounds, black boys and refugee children, were being let down by the secondary system.
He refused to blame teachers, arguing that improvements in teaching and school management had been "spectacular" in recent years and he praised test gains made in rprimary schools.
Mr Tomlinson, who stepped down as chief inspector of schools last year, is now leading a task-orce which is to report to ministers on ways to revitalise the qualifications system.
"Too many young people at 16 are underachieving, too many are not only not learning, but also not having the capacity to learn as they grow older.
"This represents a huge waste of talent and threatens our economic future and social cohesiveness," he said.
* The secondary curriculum failed to motivate all pupils.
* The burden of assessment had both limited teaching and become overly demanding for both pupils and staff.
* Performance data put the emphasis on what was measurable, undervaluing "crucial" other curriculum elements.
* The qualifications framework was also to blame. Pupils found it hard to change if they found they had embarked on the wrong course.
* Too often schools failed to give pupils good advice on future options.
* Timetabling failed to get the best out of pupils.
* There was a lack of support from parents.