Charity and youth workers surveyed almost 7,000 children over three years and found girls were far worse affected than boys.
Their self-esteem, 'emotional well-being' and satisfaction with their community sank sharply after the age of 11, continuing to get worse up to the age of 16.
Boys' happiness, meanwhile, remained far more stable.
The researchers blamed the march of technology as one of several factors making teenagers unhappy, including obvious factors like hormones and changing friendship groups.
Dr Simon Davey, Programme Leader of the Emerging Scholars' Intervention Programme, said: 'Technology and the pace of change have accelerated pressures, made them more extreme and increased competition.
'Girls in particular are more vulnerable to social pressures affecting their confidence and capability.
'Measuring well-being - one of the ultimate expressions of confidence and capability - has been difficult for us but [these] well-being tool helps us take a quantitative view for the students we work with.'
The study, carried out over three years by around 50 youth charities, is due to be released on Tuesday.
In total the charities surveyed 6,890 children aged 11 to 16 - 3,176 girls and 3,714 boys - and ranked them on eight measures of happiness.
They were overall satisfaction, self-esteem, emotional well-being, resilience and satisfaction with friends, family, community and school.
On all the measures, the children's happiness dipped after age 11 and in nearly all cases continued to fall right up to age 16.
The report said: 'By age 11, girls' emotional well-being is already below that of boys, and it keeps dropping.
'Their self-esteem levels fall away badly, while boys' remain relatively stable. Girls start off happier with their friends, but by age 16 this has tumbled below the level for boys. The research is unsettling.
'Our findings could...reflect recent concerns about the insidiousness of sexism to which girls are now subject: the profusion of sexualised imagery in everyday life; readier access to pornography; and again, new technology, and specifically the ease with which images and videos can be shared among peers.'
The research was carried out by the charity sector think tank New Philanthropy Capital, run by former Labour Downing Street adviser Dan Corry.
The report went on to add technology was not the only possible cause.
It added it was 'worrying' that Education Secretary Michael Gove is focusing more on toughness and rigour in schools, when the findings show girls need more confidence-building and support.
Anne Kazimirski from the think tank said: 'There is a powerful message for government and charities to take from this data.
'It isn't just that that young people are struggling, but that different children will have different needs.
'What works for boys as they struggle through childhood, for example, may not work at all for girls.
'If Michael Gove ploughs on without paying attention to these sorts of questions, the need for carefully-tailored help may be overlooked entirely.'
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