The Bayern Munich defender pulled ligaments in his left knee during Germany's final training session in Cologne on Thursday, ruling him out of the trip and forcing coach Joachim Low into a team rethink.
On Thursday it had been speculated as to where Lahm would fit into Low's plans.
Although the 23-year-old was certain to be on the teamsheet, he has occupied several different roles over the last few months and it was not clear exactly where he would be employed this time.
Against England last month, Lahm shone in a hitherto uncustomary position ahead of the back four.
With Bernd Schneider suspended for the Wales game, he was in line to fulfil that role again this weekend.
Instead, Low will have to implement a different strategy with Arne Friedrich and Marcell Jansen playing as full-backs and Thomas Hitzlsperger stepping into the midfield.
Bastian Schweinsteiger returns after missing the England game through injury while Lukas Podolski has the chance to play alongside his new club team-mate Miroslav Klose for the first time this year in attack.
Sporting Life.