The United boss has already put his foot down over the London 2012 tournament. Ferguson has barred any over-age player, with the exception of Ryan Giggs, from being called up by GB boss Stuart Pearce, and persuaded Mexico to give Javier Hernandez a rest.
Twenty-three-year-old Kagawa is eligible to compete but it has been confirmed the midfielder, who will join United from German champions Borussia Dortmund once he has passed a medical and gained a work permit, will not be selected.
Japanese FA technical director Hiromi Hara said: "Kagawa is one of the leading members of the Japan national senior team and he is almost certainly going to join one of the biggest clubs in the world.
"We came to the conclusion that not giving him enough rest is not good for his future nor our final World Cup qualifiers.
"I talked to Kagawa directly and told him he would not be chosen."
Ferguson already knows goalkeeper David de Gea will be part of the Spain squad, whilst Pearce is due to unveil his 18-man GB party at the beginning of next month, with Tom Cleverley and Chris Smalling amongst those young enough to play in the under-23 competition.
However, Smalling's participation would depend upon his recovery from the groin injury that ruled him out of Euro 2012.