An MRI revealed that the rookie's season is over after just nine games.
National Football League insider Adam Schefter tweeted Tuesday that the first-year receiver suffered ligament damage in his ankle during Monday's 45-21 victory over Miami and will be shut down for the remainder of the season.
The Panthers later confirmed the news that Samuel was set to have season-ending surgery.
Samuel was hurt when hurt when a defender rolled over his left ankle after an incompletion in the end zone early in the third quarter.
The Panthers will be looking for a new starting wide receiver heading into the bye week.
Samuel, 21, caught five passes for 45 yards against Miami before getting hurt.
Panthers offensive coordinator Mike Shula said the team would use a committee approach to replace Samuel.
"I think it's kind of a collective effort".
Now, with Samuel out for the season, the Panthers have to turn to others to inject that much-needed speed.
Samuel's best games came in the last 2 weeks. Samuel, a second-round pick from Ohio State, had seen his role increase in the wake of the Benjamin trade. "There's some guys on the team that would say yeah", Shula said. "Every play we've got guys going in and out, and we hardly missed a beat as far as guys going to different positions from one play to another".