Henderson, 28, made his debut for the Dragons in 2003 and, after five-year spell with the Gold Coast Titans between 2007 and 2012, returned to the Jubilee Oval 2013.
But an injury-ravaged second spell with St George Illawarra led to Henderson questioning his ability to continue playing, and he has called time on a ten-year career.
He said: “This was a very hard decision to make as I love playing and competing as a player at the highest level.
“I have had some niggling injuries, including a crook groin, that I feel were holding me back a bit on the field and this decision is one I have had to make for my family.
“It’s a shame as I would have liked to have finished the season and get a few more games under my belt with the Dragons but that’s just the way it goes.
“I would like to thank both Steve Price and CEO Peter Doust for allowing me the opportunity to re-join the club and for understanding my reasons in leaving.”
Henderson hopes continue playing in the local Illawarra league and pursue an apprenticeship to become an electrician.