IPPR North analysis shows that areas such as Humber (65 per cent leave), Tees Valley (64 per cent leave) and the Sheffield city region, which also includes Doncaster, Rotherham and Barnsley (62 per cent leave) are most likely to experience Brexit "turbulence".
But the think-tank said establishment figures should not dismiss northern Brexit voters as "foolish or simple" and instead understand their decision was a "cry of community outrage" at wealth and power inequality.
"To conclude that the North's vote to leave was an act of collective self-harm is to completely misunderstand what it is to be northern," IPPR North director Ed Cox said in a speech on Friday.
"It has made me very angry that since the referendum, when it has become clear that the northern economy could suffer significantly as a result of the Brexit decision, that some in the metropolitan media have presented northerners as foolish or simple.
"We believe that Brexit is a cry of community outrage at the imbalances of wealth and power, played out in glorious Technicolor within and between the regions of this nation.
"Scotland had already had its say, in June it was a chance for England to rise up against the wishes of the Westminster elite."
At its annual State of the North conference, IPPR North will present new research showing that northern regions are more than twice as dependent on EU trade as London.
The analysis shows the North's economy is already increasingly "decoupling" from London and Scotland and the capital is a "great deal" more insulated from the Brexit effect.
"Add to this the loss of EU funding for our universities and most deprived places, add to this the impact of fewer migrants in an ageing population, add to this the impact on our rural economy and whatever kind of Brexit we end up with, it looks a pretty challenging place from here," Mr Cox will say.
IPPR North called for a northern Brexit negotiating committee to feed the North's voice into the Government's strategy and an expansion of the "northern powerhouse" initiative away from prosperous cities like Manchester and Leeds.
Mr Cox insisted the Brexit vote was as much a vote to "take back control" from Westminster as from the EU.
"Anybody who listened to Melvyn Bragg's brilliant documentary series The Matter of the North will have been reminded that the North of England has a rich history and tradition of taking back control," he said.
"In simple terms, just like our Scottish neighbours, northerners have historically compromised short-term economic benefits for the sake of their wider freedom and autonomy. This I believe is what we are witnessing in the Brexit vote. The 80-year experiment with centralisation is over, and it is little wonder the Establishment are struggling to get it."