Murphy, who injured the knee while fielding his position Wednesday night at Triple-A Buffalo, will not require surgery, but will miss the remainder of the season.
Murphy only arrived at Buffalo late last month, following a disabled-list stint to repair a sprain of the same knee. In his absence, the Mets promoted rookie Ike Davis, who took over everyday duties at first base on April 19. Mike Jacobs started the season as the Mets' first baseman.
Murphy was playing only his second game at second base, in an attempt to become more versatile and work his way back to the Mets in a utility role. Earlier Wednesday, manager Jerry Manuel said he did not consider Murphy a candidate to replace Luis Castillo, who may need to go on the disabled list with multiple foot injuries.
The Mets had no update on Castillo, who was also examined by doctors Thursday.
Fielding his position on a double-play attempt Wednesday night, Murphy had to be carted off the field after a Syracuse runner took him out with his slide.
Murphy hit .266 with 12 home runs as the Mets' regular first baseman last year, his first full season in the big leagues.
Anthony DiComo is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.