The Hull City midfielder and former England international suffered a fractured skull when he collided with Chelsea’s Gary Cahill during a match at Stamford Bridge in January 2017, and has not been allowed to play since.
He had been working towards a comeback, but announced on Tuesday he was retiring on doctors’ advice.
He said he had “no option” but to bow out, thanking the support of his “incredible” teammates, family and friends.
“I can confirm that following specialist medical advice I am having to retire from playing professional football,” he said.
“I have worked tirelessly in order to be able to return to the pitch. Unfortunately, having taken expert medical advice I now have no option but to retire due to the risks involved given the nature of my injury.
“I am and always will be eternally grateful for the incredible network of people around me who have helped me to recover from what was a life-threatening injury in January 2017.”
Mason added: “I am so proud to have come through the ranks to play for my club, the club I love.
“To have had the honour of captaining the team fills me with immense pride.
“Thank you to all of my teammates over the years – there are too many to mention. It’s been a privilege to play alongside you all.”
Mason made a total of 69 Premier League appearances after breaking into the first team at Tottenham in 2014, before signing for Hull two years later.
A statement on Hull’s official club website read: “Ryan would like to put on record his thanks to all at the club who have aided his recovery to this point and he his is indebted to them for their support and compassion over the past 12 months.”