Jonny Wilkinson will be out for four to eight weeks after a scan confirmed he has torn the medial ligament in his right knee.
Wilkinson has had a dreadful run of injuries since 2003
Wilkinson suffered the injury in an innocuous tackle in Newcastle's match against Worcester on Friday.
England's next match is against New Zealand on 5 November and Wilkinson seems sure to miss out.
"I've gone past the stage of saying 'Why me... why does it always happen?'" said Wilkinson.
"I know some people will start thinking about what that means regarding the autumn international season.
"I guess it does not augur well but to be honest thoughts of England are miles away.
"I've started to come to terms with my situation.
"I accept the injuries more quickly and rather than wasting mental energy feeling frustrated I'm instead thinking 'What can I do to cut down the rehab time.'"
I heard quite a rigorous pop when it happened
Wilkinson was speaking to the Times newspaper, and he confirmed that the injury is the same one he previously suffered to his left knee.
"It's a grade two partial medial ligament tear. It took me nine weeks to come back from the last one.
"I heard quite a rigorous pop when it happened, a noise I recognised from when I'd injured my left knee.
"When I stood up I had that same loose feeling around the joint so I knew pretty much immediately what had happened.
WILKO'S TALE OF INJURY WOE
Sep 2006: Tears medial ligament in right knee
Feb 2006: Damages right abductor groin muscle in training; requires surgery
Nov 2005: Tears muscle in groin, which restricts his daily kicking practice
Aug 2005: Suffers appendicitis on pre-season tour of Japan
Mar 2005: Injures same knee on comeback v Harlequins
Jan 2005: After December return, suffers medial ligament damage against Perpignan
Oct 2004: After return in August, suffers haematoma in upper right arm
Feb 2004: Requires operation, misses rest of season
Dec 2003: Forced off in first club game after World Cup; Learns he has a long-standing shoulder/neck condition
"I knew I couldn't play on, I was just keen to get off the field and get it iced."
This new injury is the latest in a long line of problems that Wilkinson has had to endure since kicking England to World Cup glory in 2003.
Neck, groin, abductor, biceps and two knee ligament injuries have restricted him to just 15 Premiership starts since that night in Sydney.
He did make the Lions tour to New Zealand in the summer of 2005, but has not played for England since the World Cup.
Before the start of the new Premiership season last weekend, Wilkinson said he had changed his kicking style in an attempt to end his injury nightmare.
Newcastle rugby director John Fletcher said: "We are bitterly disappointed for him because he had finished last season so well, had an excellent pre-season and then started brightly again this time around.
"It was a freak accident really, but these sorts of industrial injuries are not uncommon in rugby and we look forward to having him back again fully fit."