He took to Instagram to make the announcement on Monday morning, posting a collage of photos of his children with the caption "I've missed way too much for way too long.and I'm done. Many thanks to my family, coaches, the fans, and everyone who played a role in my football life", he wrote on Instagram.
Harrison played almost his entire career with the Steelers and the 84.5 sacks he collected while wearing black-and-gold are a franchise record.
Harrison helped the Patriots reach the Super Bowl, where they ultimately lost to the Philadelphia Eagles.
Harrison, 39, played a total of 15 seasons in the league, spending 13 years with the Steelers during two spells.
Father Time appeared to finally get the better of Harrison in 2017, though. He returned to Pittsburgh after injuries decimated the team's linebacker group and in his second act became a valuable leader on the field and elsewhere, often including teammates in his draining (and well-documented) offseason workout regiments in Arizona.
James Harrison calls it quits again.
At a position where few last into their mid-30s, Harrison continued to thrive.
Harrison will be most commonly remembered for his exploits as part of the Pittsburgh Steelers, even though he ended his career with the New England Patriots. He played sparingly for much of 2017 and the Steelers granted him his release in December.