The 39-year-old pass rusher announced on Instagram on Monday morning he is calling it a career.
"I've missed way too much for way too long," Harrison wrote. "I'm done. Many thanks to my family, coaches, the fans, and everyone who played a role in my football life."
Harrison, who turns 40 next month, previously reneged on a retirement back in 2014, when he returned to the Steelers less than three weeks after stepping away.
If this is indeed the end, the pass-rusher concludes an amazing NFL journey.
The Kent State product went undrafted in 2002, with most teams believing he was too small to be a pass rusher. To prove himself, Harrison played for NFL Europe's Rhein Fire in 2003. He eventually became an NFL Defensive Player of the Year, five-time Bowler and two-time first-team All-Pro in Pittsburgh.
As a relentless rusher with the brute strength of 45 brown bears and a good first step, Harrison worked his way to become the Pittsburgh Steelers' all-time sack leader, with 80.5.
Harrison played his first 10 NFL seasons with the Steelers before a one-year sabbatical with the Cincinnati Bengals (where he famously loathed and taunted Hard Knocks cameras). The linebacker then returned to Pittsburgh in 2014, where he played until being cut midway through last season. Harrison famously signed with rival New England Patriots for the stretch run. He started the Pats' Super Bowl LII loss.