Germany striker Mario Gomez, making a rare start instead of Miroslav Klose, scored a fine solo effort and Andre Schuerrle doubled the lead as the hosts enjoyed long spells of attacking football in the first half.
Walter Gargano pulled one back minutes after the restart with a close-range effort after the German defence failed to clear as both coaches made several substitutions.
"There were many things I liked in our game today, especially in the first half," said Germany coach Joachim Low.
"There was a lot of pace, something we had not expected (after the end of the Bundesliga season).
The match, less than a year after their 2010 World Cup third place play-off which Germany won 3-2, was a warm-up for Germany's Euro 2012 qualifiers in Austria and Azerbaijan and for Uruguay ahead of the Copa America in July.
"We made some mistakes and paid the price. Obviously we wanted to do well against the Germans," Uruguay's Diego Forlan told reporters.
Muslera spectacularly palmed a 30-metre dipping shot from Toni Kroos over the bar but could do nothing to stop Schuerrle's curled shot providing the 20-year-old his first international goal on his third appearance.
