The visitors, missing more than half their usual starting line-up with eight Bayern Munich players set to join the squad later on Saturday, looked a long way from being ready to challenge for their first major trophy since 1996.
Poor defensive organisation, a lack of their usual offensive spark and a sloppy passing game caused Germany to slump to their biggest defeat by Switzerland since their first clash in 1908 ended in the same result.
"We made far too many mistakes," said Germany coach Joachim Low, who will announce his final squad next week.
"I did not expect this result though I knew it could be dangerous because of the many training sessions we have had until now. I knew that we could be lacking this freshness," he told reporters.
"The team had not played with such a line-up before. Now we have two weeks to work on this and I have absolutely no concerns that the this coordination within the team will start working."
The Germans, taking on Portugal, Netherlands and Denmark in the tournament starting in Poland and Ukraine on June 8, fell behind after 21 minutes with new Hoffenheim signing Derdiyok taking full advantage of a gaping hole in the opposing defence to slot in a cross by Tranquillo Barnetta.
He struck again two minutes later, heading in another pin-point Barnetta cross as central defenders Mats Hummels and Per Mertesacker, making his comeback from an injury that kept him out since February, struggled to gel.
Derdiyok could have added another a minute later but was foiled by keeper Marc-Andre ter Stegen, making his international debut in the absence of first choice Manuel Neuer.
The Germans upped the pressure and were rewarded just before the break when Hummels headed in a Mesut Ozil free-kick and Andre Schuerrle pulled another back for the Germans after Derdiyok headed his third goal in the 50th minute.
Both sides added another with Switzerland, who failed to qualify for Euro 2012, scoring through Stephan Lichtsteiner and Germany's Marco Reus hitting back.
Admir Mehmedi completed a frantic spell of four goals in 12 minutes when he slotted in following another feeble defensive effort by the Germans and the Swiss also hit the bar in the dying minutes.
Swiss coach Ottmar Hitzfeld, a German, said the heavy defeat could be a good sign for his countrymen.
"It is a good omen because we [Swiss] were also the only team to beat Spain [at the 2010 World Cup] and then they went on to win the title," said Hitzfeld.
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