Walcott suffered the injury late in the 2-0 victory over Tottenham Hotspur in the FA Cup third round on Saturday and he left the field on a stretcher after appearing to jar his knee in a challenge with Danny Rose.
The 24-year-old did not appear in too much discomfort and caused controversy by indicating the score to Tottenham fans behind the goal as he was carried off.
The Football Association took no action over Walcott's gestures but any relief at avoiding disciplinary action was quickly overshadowed by the medical bulletin which revealed he had ruptured anterior cruciate ligaments in his left knee.
"Theo will have surgery in London in the near future and is expected to be out for at least six months, therefore missing the remainder of the season and the World Cup in Brazil in the summer," Arsenal said on their website.
Walcott, capped 36 times by England, missed two months of this season with an abdominal injury and had looked in great form since returning, scoring five goals in five games before Saturday's derby.
His absence will be keenly felt by Premier League leaders Arsenal as they try to maintain their title challenge and will also be a major blow for England manager Roy Hodgson.
"Everyone at Arsenal wishes Theo a speedy recovery and we look forward to seeing him back on a football pitch as soon as possible," the club said.
Walcott, aged 17, was an unused member of England's squad for the 2006 World Cup finals in Germany and was surprisingly left out of the squad for the 2010 tournament in South Africa.
(Reporting by Martyn Herman, editing by Ed Osmond)
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