With Jerome Boateng suspended following his sending-off against Sweden, Mats Hummels returns to the centre of defence alongside Niklas Suele - the Bayern defender also earning his maiden World Cup start.
Four-time winners Germany, who had not been eliminated in a World Cup first round since 1938, were a shadow of their once dominant selves, managing only two goals in their three group games.
Italy had won back-to-back World Cups before the Second World War got in the way, and much had changed by the time the 1950 tournament came around in Brazil.
Italy have historically been slow starters in World Cups. Pele, though, picked up injuries after Brazil's match against hard-tackling Bulgaria and had to sit out their second game against Hungary.
Still, Spain had lost their opening match to Switzerland in 2010 and went on to win the title.
Germany's elimination from the World Cup at the first hurdle and dismal performances in Russian Federation could see calls for that dreaded hallmark of summer failure: the root and branch review.
Khedira replaces Sebastian Rudy in midfield after Rudy was sidelined with a broken nose suffered against the Swedes and will partner Toni Kroos, who hit Germany's last-gasp victor against Sweden.
Vicente del Bosque's team arrived in South America having won 3 consecutive major tournaments between 2008 and 2012, but this proved a step too far for a side lacking the hunger of old.
In France's next match, they drew 0-0 against Uruguay, again without Zidane.
The 2014 champions, who needed a win in their final game to advance to the round of 16, ended bottom of Group F after a shock 2-0 defeat to Korea Republic on Wednesday afternoon. But this exit resulted in an outpouring of sympathy for the Spanish team with the likes of Iker Casillas, Xavi Hernandez, Xabi Alonso and David Villa all retiring from global duty after that.