The Manchester United star suffered a groin injury during the 2-0 defeat to Chile at Wembley on Friday evening.
The 21-year-old, who started at centre-back alongside Gary Cahill, was replaced by his United team-mate Chris Smalling after 57 minutes.
He has now undergone a scan on the injury and has returned to his club for further treatment.
A statement from the FA read: "Phil Jones has been ruled out of England's final match of 2013 against Germany on Tuesday evening.
"The Manchester United defender picked up his injury during England's defeat to Chile on Friday evening, and following a scan today (Saturday) he has returned to his club."
Cahill is now likely to resume his partnership with Phil Jagielka in the heart of the England defence against Germany.
Boss Roy Hodgson gave the players Saturday off to recharge their batteries ahead of Tuesday's game.
Hodgson is hopeful that Steven Gerrard, Daniel Sturridge, Kyle Walker and Rickie Lambert will all be available after missing the game against Chile.
Joe Hart, Ashley Cole and Andros Townsend are also expected to return to the starting XI.
Hodgson is confident his side will learn the lessons from their defeat against Chile at Wembley, when boos rang around the stadium as England's 10-match unbeaten run came to an end.
"We used a lot of players and debutants and players who haven't got many caps," said Hodgson.
"Going a goal behind early meant we were on the back foot and always chasing the game against a team who were more than capable of keeping us at bay and keeping the ball.
"It would be harsh to make too many judgements on them (the debutants). They came into a team where a lot of people around them weren't that experienced if we take Frank Lampard out of the equation.
"Even our more experienced players would have found it difficult anyway because Chile were good and deserved to win.
"They played excellently. We learned a lot about South American opposition and how good they are at sucking you towards their goalkeeper and then manage to ping 50-yard balls on to people's toes. That's one of the best displays of goalkeeper passing I've ever seen.
"It's important that having been knocked down they pick themselves up again. We have another big game on Tuesday night. There are lessons to be learned. We need to play better if we are going to beat top teams like Chile and Germany."