Real Madrid midfielder Khedira has missed the majority of the campaign with a cruciate ligament injury sustained in Germany's friendly with Italy back in November last year.
The 27-year-old has not featured for his club since, although he has been an unused substitute in the Spanish side's last two domestic matches.
However, Germany coach Joachim Low has decided to take a gamble on Khedira as Germany look to win the World Cup for the fourth time in their history.
But one player whose injury problems have seen them left out is Fiorentina striker Mario Gomez, whose debut season with the Italian club has been blighted by fitness issues.
Gomez has played just 15 times in all competitions for Fiorentina this term, and Low insisted that was not enough for him to be considered for selection.
"I wanted him (Gomez) to be fit," Low said. "But he's only played around 280 minutes since September and I don't think he's ready for the tournament."
Miroslav Klose has also seen his 2013-14 campaign hampered by injuries but the Lazio striker has been included in the squad, and Low has faith that can continue the fine form he has displayed at previous World Cups.
"Miro is Germany's record goalscorer at the World Cup he can become the most successful World Cup striker in football history," Low added.
"He has shown throughout his career again and again that he is able to prepare in a short time. I have no doubt that he will succeed again."
There are few surprises in the squad, which features a total of seven Bayern Munich players and six from Borussia Dortmund.
Hannvoer's Ron-Robert Zieler has been preferred to Marc-Andre Ter-Stegen as the third-choice goalkeeper, while Hoffenheim's Kevin Volland earns a place in the squad due to what Low labelled as a "dramatic improvement".
Schalke duo Maximilian Meyer and Leon Goretzka will be among the youngsters look to make an impression ahead of the announcement of the final 23-man squad, which will be confirmed on June 2.
Germany will start their preparations for the tournament with a training camp on May 21, taking on Cameroon in a friendly on June 1 before flying out to Brazil six days later.
Squad in full:
Goalkeepers: Manuel Neuer (Bayern Munich), Roman Weidenfeller (Borussia Dortmund), Ron-Robert Zieler (Hannover).
Defenders: Jerome Boateng (Bayern Munich), Erik Durm (Borussia Dortmund), Kevin Grosskreutz (Borussia Dortmund), Benedikt Howedes (Schalke), Mats Hummels (Borussia Dortmund), Marcell Jansen (Hamburg), Philipp Lahm (Bayern Munich), Per Mertesacker (Arsenal), Shkodran Mustafi (Sampodria), Marcel Schmelzer (Borussia Dortmund).
Midfielders: Lars Bender (Bayer Leverkusen), Julian Draxler (Schalke), Mario Gotze (Bayern Munich), Leon Goretzka (Schalke), Andre Hahn (Augsburg), Sami Khedira (Real Madrid), Toni Kroos (Bayern Munich), Maximilian Meyer (Schalke), Mesut Ozil (Arsenal), Bastian Schweinsteiger (Bayern Munich), Matthias Ginter (Freiburg).
Forwards: Thomas Muller (Bayern Munich), Lukas Podolski (Arsenal), Marco Reus (Borussia Dortmund), Andre Schurrle (Chelsea), Miroslav Klose (Lazio), Kevin Volland (Hoffenheim).
