The 20-year-old featured as a substitute in the midweek Europa League win over FC Sheriff, but was not passed fit for the European Championship qualifiers against Finland on Thursday and San Marino the following Tuesday.
Kane's absence is a further setback for manager Gareth Southgate, as Spurs midfielder Tom Carroll and Norwich City winger Nathan Redmond have also been ruled out through injury.
Captain Andre Wisdom is another absentee due to suspension as England attempt to tighten their grip on top spot in Group One.
Manchester United's young striker Will Keane has been invited to train with the U21s as he continues his recovery from a serious knee injury.
Keane suffered the injury while playing for England U19s back in May 2012, but is finally nearing full fitness and Southgate is glad to include the 21-year-old in training.
Southgate told the Football Association's official website: "I've invited Will along to join us for training this week and it's great to see him back.
"He suffered the injury when he was playing for England last year, so I'd like him to feel that he's in our thoughts.
"He's back playing for United now, so if this can help him in his rehab and get re-acquainted with his England squad mates then we're more than happy to help."