Karnezis started the 2016–17 season as the undisputed first-choice goalkeeper for the club. On 11 December 2016, he put on a superb performance as Luigi Delneri’s men managed to win where teams like Roma couldn’t. If the 3–1 scoreline was harsh on Atalanta, it's because La Dea had a myriad of chances, but Karnezis denied plenty of goals. Without the keeper's wonder saves, the game could have gone very differently. In at least five cases he was superb, even stopping from his own teammate Silvan Widmer. On overall, in December 2016 Karnezis had only been forced to pick the ball out of his own net once in the last four matches, with clean sheets against U.C. Sampdoria, F.C. Crotone and Bologna. On 5 February 2017, in a 0–0 away draw against Chievo, Karnezis reached 100 appearances with the jersey of the club in all competitions. On 19 February 2017, in a frustrating defeat against Sassuolo, he reached 100 appearances in the jersey of Udinese in Serie A, in a game where the Greek international performed a desperate double save on Matteo Politano and the Federico Ricci follow-up. On 12 March 2017, in a 3–1 away win against Pescara, he suffered an injury and replaced by his teammate Scuffed. Karnezis was diagnosed with a dislocated finger and a micro-fracture at the base of his right little finger. His hand was immobilised with a cast for the next three weeks. On 9 April 2017, he returned to the squad in a 3–0 Serie A home game against Genoa C.F.C.