The 32-year-old was unable to play a full part in training in Malahide on Thursday morning and the decision has been taken that he will not be involved in the game at the Aviva Stadium on Friday.
However, he has not given up hope of making Tuesday's trip to the Faroe Islands.
The Football Association of Ireland confirmed the development via its Twitter feed, saying: "Robbie Keane has been ruled out of the Germany game with an Achilles injury.
"Will hopefully be fit for Faroes."
Keane joins fellow striker Kevin Doyle, central defensive partners Richard Dunne and Sean St Ledger, and midfielders Glenn Whelan and James McClean on the sidelines for the home game against the Group C leaders.
Stoke City's Jonathan Walters will instead start alone up front with Seamus Coleman and Keith Fahey coming into the side along with Keith Andrews, who returns from suspension. Sunderland defender John O'Shea deputises as captain.
Ireland team to face Germany: Westwood, Coleman, O'Shea, O'Dea, Ward, McCarthy, Andrews, Fahey, McGeady, Walters, Cox.