Cazorla has been out sidelined since October 16 after injuring his right ankle in Arsenal 6-0 win over Ludogorets in a Champions League tie.
He was expected to return in early 2017 but underwent a surgery when the injury refused to heal on its own.
He was expected again to return in March but Wenger has revealed that the midfielder will not play again this season.
“The season is over for him,” Wenger said on Thursday in a press conference ahead of Arsenal’s home clash against Manchester City.
This is the second time the 32-year-old will miss the large chunk of a football season.
In the 2015/2016 season, the midfielder was sidelined in November before returning only for the final fixture of the season.