Griffin, who had his left hand amputated at age 4 because of amniotic band syndrome, a congenital condition, became the first player with one hand to be drafted in the NFL's modern era when the Seattle Seahawks chose him in the fifth round in 2018. It reunited him with his twin brother, Shaquill, then the Seahawks' starting left cornerback.
The NFL congratulated Griffin on his retirement, tweeting that he is "a true inspiration."
Shaquem Griffin was waived by the Seahawks in 2020 and said Wednesday that his brother stayed with him and skipped practice the next day. His biggest worry was about how he would be perceived.
"I didn't want people thinking, Aw, the one-handed player got cut. I don't do sympathy, man. I don't like people feeling sorry for me," he wrote. "But at no point did I ever think that that was it for me in the NFL."
Griffin, 27, was signed to the Seahawks' practice squad after being waived and promoted to Seattle's active roster later that season. He appeared in 46 games with the Seahawks in three seasons and had nine tackles, three quarterback hits and a sack. Griffin also had a sack of Aaron Rodgers in the divisional round of the 2019 season, leading to a memorable moment of Shaquem taking down the Green Bay Packers quarterback just before Shaquill arrived then the brothers celebrating with each other afterward.
The Seahawks congratulated Griffin on his retirement Wednesday and tweeted: "Your story will be remembered for generations."
Griffin signed as a free agent with the Miami Dolphins last year but was released before the season. He had tryouts with several other teams after that but said Wednesday that he realized that he wanted to play in the NFL only if he was playing alongside his brother, who is now on the Jacksonville Jaguars after signing as a free agent last year.
"I worked out for the Cardinals, the Titans and the Jets, and then I got calls from Buffalo, Dallas and Atlanta. But after that Jets workout, I realized something. All this traveling around, working out for teams, trying to catch on somewhere, trying to hang on -- it wasn't what I wanted. Football had already given me so much, and the only thing I still really wanted from the game was to play with my brother again," he wrote.
He said in his Players' Tribune piece that, "Football was always Plan B."
Griffin said his father told him and his brother that "Plan A was to go to college, get an education and do something that would make a positive impact in the world."
He said he met with NFL commissioner Roger Goodell at the Super Bowl and received an invitation to join the NFL Legends Community, and it was in a conversation with Goodell and other former players in the program that he realized the positive impact he can have on others.
"I know the positive effect I'm having on others," Griffin wrote. "I'm speaking at colleges and universities, talking to football teams and even presenting to corporate America about never doubting yourself and tirelessly pursuing your dreams. People at companies want to hear what I have to say when actually I'm the one that can learn so much from them. It's crazy."
Griffin thanked former UCF coach Scott Frost for giving him a chance to play for the Knights, Seahawks coach Pete Carroll and his staff and his former Seahawks teammates such as Bobby Wagner and K.J. Wright for the mentorship they provided.
He saved his final thank-you for his brother.
"We've always said, 'We live through each other.' That won't change. I'm still with you, living through you every time you take the field,'" he wrote.
"So keep ballin' out. Keep living that dream. We've been told countless times, and it's still humbling every time I hear it, that there should be a movie about our journey together, and what we've been through, together, always inseparable. Maybe that day will come sooner than later. But until then, I'm gonna go build something new so I can do what Dad always told us to do: leave the world a better place than when we found it.
"On to Plan A."
ESPN's Brady Henderson contributed to this report.