The letter was signed by leaders from Greater Manchester, Liverpool, North East, Sheffield, and West Yorkshire combined authorities.
It requested a meeting with Theresa May, who has not yet commented, "at her earliest convenience".
It stresses it is "vital" the north's voice is heard "loud and clear".
It pointed out the region had a "significantly larger" economy than Scotland and Wales and a population greater than London.
Greater Manchester's interim mayor Tony Lloyd sent the letter on behalf of himself and leaders of the Liverpool City Region Combined Authority, North East Combined Authority, Sheffield City Region Combined Authority and West Yorkshire Combined Authority.
The letter noted Ms May's talks with Scotland's First Minister Nicola Sturgeon in Edinburgh and invited her to a similar meeting in Greater Manchester "to discuss our role within the Brexit negotiations".
It read: "The north of England has long had concerns that we are being ignored, caught between an economically and politically powerful London and an increasingly politically important Scotland."
It continued: "As we negotiate our exit from the European Union, you have made clear that you believe in having an approach and negotiation objectives that include the whole of the United Kingdom.
"On that point we wholeheartedly agree.  It is absolutely vital that the voice of the north of England is heard loud and clear."
The combined authorities were set up as part of the government's devolution agenda.
This led to the Northern Powerhouse strategy, brainchild of former Chancellor George Osborne, an attempt to corral the north's population of 15 million into a collective force that could begin to rival that of London and the South East.
There has been some uncertainty over its continuation following Mrs May's reshuffle and Mr Osborne's return to the back benches.
However, Conservative MP for Brigg and Goole Andrew Percy was appointed as the new Northern Powerhouse minister on Sunday and a government spokesman said the Northern Powerhouse would "continue to be a priority".
Leaders of five combined authorities have written to the prime minister saying the north of England needs a "strong voice" in Brexit negotiations.