The one-cap Wales international has been with the Sharks since 2005, making over 200 appearances for the club during that time.
Lewis-Roberts has been unable to fully recover from the damage suffered 13 months ago, however, and has therefore been forced to call time on his career at the age of 36.
"It's sad that I have had to admit defeat to this knee injury," he told Sale's official website. "I was enjoying my rugby as I always did in the game at Bristol and I made a tackle which caused the damage."
Sale director of rugby Steve Diamond said: "What a great servant Eifion has been for the club. He will be remembered for the 100% effort he put in each and every game."
Lewis-Roberts, who made his debut during the Premiership winning season in 2006, will now take on an ambassadorial role with the Sharks.