"I decided I'm hanging up the cleats and I'm looking forward to the next chapter in my life," Mercilus, 31, said in a video he posted on Instagram.
The 2012 first-round pick played all but four regular-season games in his career with the Texans, before he was released by the team in October. Mercilus signed with the Green Bay Packers but tore his left biceps on Nov. 14. He was placed on injured reserve but was able to return for a playoff game.
The pass-rusher's best season came in 2015, when he had a career-high 12 sacks.
In 138 career games, Mercilus had 362 tackles, 58 sacks, 13 forced fumbles and two interceptions. His 57 sacks for the Texans rank second in franchise history behind J.J. Watt, who had 101 sacks with Houston.