Rivera, baseball's all-time saves leader, collapsed on the warning track after leaping in an attempt to catch a fly ball and had to be taken off the field on a cart.
He was transported to a hospital for an MRI and after New York's 4-3 loss to Kansas City. Yankees Manager Joe Girardi said he had been told by doctors Rivera had a torn ACL in the knee.
"You lose a Hall of Famer," Girardi said moments after the New York locker room was opened to media members. "If that's what it is, that's as bad as it gets."
Girardi said Rivera would return immediately to New York for additional evaluation.
Rivera, 42, was in the outfield running down fly balls while his teammates were taking turns in the batting cage prior to New York's game, something he has done throughout his career.
He jumped near the wall in an attempt to catch a ball and when he came down his right knee gave way. He fell to the ground in obvious pain.
Rivera has 608 career saves, most in baseball history. He has five saves in six opportunities in this, his 18th season with the Yankees. Rivera has posted a 1-1 record with a 2.16 ERA in 2012.