The Ulster flanker was hurt during the RaboDirect PRO12 26-3 win over Zebre on Friday night.
An MRI scan has confirmed he suffered a cartilage tear to his right knee.
"The injury will require surgery and will rule Chris Henry out of playing for approximately four weeks," the Irish Rugby Football Union said on Monday.
Munster back rower Tommy O'Donnell has been called into the squad as cover.
Centre Gordon D'Arcy and wing Simon Zebo have also been ruled out for the remainder of the competition, while fly-half Jonathan Sexton and lock Mike McCarthy will miss Sunday's clash with Scotland.
Concerns also remain over the fitness of centre Brian O'Driscoll and second row Donnacha Ryan, while prop Cian Healy has been ruled out of the games against Scotland and France through suspension.
Meanwhile Leinster's Ian Madigan has been called into the Irish camp after Connacht centre David McSharry was declared unavailable due to a groin injury.