The school announced on Wednesday morning that the junior "had surgery this morning to repair his ACL and will miss the rest of the season."
The surgery was done on his right knee. He suffered a torn ACL in his left knee during the Cardinals second game last season.
Lamb's 97-yard kickoff return against in the season-opener sparked U of L's 31-13 win over visiting Miami on national television.
"I don't even remember getting touched," he said following the win. "I just remember hitting it."
Clocked as the fastest member of the Cardinals roster, Lamb had returned 6 kickoffs with a team-leading 31.2 average per attempt.