The Football Association and the Professional Footballers' Association will invite applications for independent research into whether there is any evidence to show a link between players suffering dementia later in life after a career in the game.
The family of former England and West Brom forward Jeff Astle have long campaigned to raise awareness around brain injury in football.
Astle, scorer of West Brom's winner in the 1968 FA Cup final and a cult hero among Albion fans, died in 2002 aged 59 from chronic traumatic encephalopathy (CTE) linked to repeatedly heading heavy leather footballs.
The joint announcement from both the game's governing body and the players' union follows months of consultation and analysis.
It was confirmed in Thursday's statement that the Expert Concussion Panel, which was established in 2015, has now "agreed the parameters of the research, which will be completed by an independent research group".
The focus of that independent study is to be on one fundamental question, namely: "is the incidence of degenerative neurocognitive disease more common in ex-professional footballers than in the normal population?"
The closing date for submission of initial research proposals is May 2017.
The FA's head of medicine, Dr Charlotte Cowie, said this was "a crucial issue" for the organisation, and "one that we feel passionately about addressing."
"Dementia is a debilitating disease, which places extraordinary emotional and physical burdens on both sufferers and those close to them.
"Player welfare is paramount and it is increasingly important that the football authorities investigate further whether there are any potential risks associated with heading the ball, as this is a unique feature of our game."
The FA and PFA will jointly fund the project, believing credibility and resources will be added by the collaborative approach.