"I've missed way too much for way too long ... and I'm done," Harrison wrote on Instagram. "Many thanks to my family, coaches, the fans, and everyone who played a role in my football life. #2ndAndFinalRetirement. #HarrisonFamilyValues. #BlessedAndHighlyFavored. #GodsPlan."
"Deebo" included photos of his two sons on his retirement posts.
Harrison, 39, was the 2008 NFL Defensive Player of the Year. He made the Pro Bowl five times and was named an All-Pro twice during his 15-year NFL tenure.
Pittsburgh signed the Kent State product in 2002 as an undrafted rookie free agent. He played his first 10 seasons for the Steelers, before joining the Cincinnati Bengals in free agency in 2013. Harrison returned to the Steelers in 2011. He signed with the New England Patriots last offseason.
The 6-foot, 242-pound defender won a Super Bowl with the Steelers in 2009. He also appeared in the Super Bowl in 2011 with the Steelers and in February with the Patriots.
Harrison had 84.5 sacks, 34 forced fumbles, 26 passes defensed, nine fumble recoveries, eight interceptions and a touchdown in 193 career appearances. Harrison ranked No. 7 in the NFL on the list of active sack leaders.