Hornby, the Dragons' record holder for games played with 271 first-grade appearances, said his body told him he'd had enough.
The 32-year-old, who has only played with the Dragons, said he came to his decision last week and informed his teammates of his call following Monday night's 32-22 loss to North Queensland at WIN Stadium.
That loss signalled the end of the Dragons' faint NRL finals hopes.
"It is a difficult time and decision to walk away from the game but, having played footy since I was nine and had 13 seasons in first grade, I have decided that it's time to move on," Hornby said.
"Whilst physically I could probably continue, mentally I have had enough."
Hornby admitted the obvious highlight was leading the joint venture to its first premiership in 2010, while also claiming his NSW Origin and Australian Test jumpers held a special place in his heart.
