The Everton left-back would have been expected to start for his country in Saturday's Euro 2016 qualifier with Slovenia, with a friendly to come against Scotland three days later.
However, the 29-year-old will now return to his club after sustaining an injury on the eve of the clash with Slovenia at Wembley.
"Leighton Baines is to return to Finch Farm after withdrawing from the England squad through injury," read a statement on Everton's website.
"The left-back sustained the problem in training on Friday and will now miss the games against Slovenia and Scotland."
Midfield duo Michael Carrick and Andros Townsend have also withdrawn from Roy Hodgson's squad this week due to injuries.
Arsenal's Kieran Gibbs is set to step in at left-back as England seeks to maintain their 100 per cent start to Group E.
