Martinez suffered the injury during Manchester United's 2-2 draw with Sevilla in the Europa League on Thursday.
The 25-year-old has made 45 appearances in his debut season at Old Trafford, scoring one goal and has been indispensable at the back.
Manchester United manager Erik Ten Hag was left concerned when Martinez left the field shortly before full time against their Spanish opponents and his fears have now been confirmed.
A United statement confirming the news read: "Lisandro Martinez has been ruled out for the remainder of the season after fracturing a metatarsal bone in his foot.
"However, the Argentinian defender is expected to make a full recovery in time to be ready for the start of next season."
In the same game, United lost another central defender Raphael Varane to injury.
Earlier on Friday, Ten Hag reiterated his confidence in the rest of his centre backs as he is set to choose between Harry Maguire, Victor Lindelof and Luke Shaw to fill the roles for the time being.
"I have a lot [of faith]," said Ten Hag. "I think I have decent centre-halves and they proved that in the past, they have proved this season.
"I think we have four or five very good centre-halves who can do the job."
Manchester United are in action against Nottingham Forest on Sunday.
