The left-hander has not started since September 2 against the Atlanta Braves when he came out after five outstanding innings because of a strained pectoral muscle.
"An MRI at the Hospital for Special Surgery in Manhattan yesterday revealed that ... Santana has suffered a tear of the anterior capsule of the left shoulder," the Mets said in a statement.
"The injury is located on the front and bottom part of the shoulder close to the pectoral muscle, resulting in discomfort radiating through both the pectoral muscle and shoulder."
The Mets said the 31-year-old would have surgery "in the near future" and was expected to resume throwing in the spring.
Venezuela-born Santana, a two-time winner of the Cy Young Award as the American League's top pitcher, will have to spend his third consecutive off-season recovering from surgery.
Santana was 11-9 with a 2.98 ERA in 29 starts in 2010, having pitched 199 innings.
(Writing by Mark Lamport-Stokes in Los Angeles; Editing by Steve Ginsburg)