Organisers said 250,000 people took part in the rally; police put the figure at around 100,000.
Opponents of the Transatlantic Trade and Investment Partnership (TTIP) say it is undemocratic and threatens consumer and worker rights.
But supporters of the deal, which lowers trade barriers, say it would boost economies and create jobs.
Hundreds of buses shuttled protesters to Saturday's demonstration in the German capital.
"We are here because we do not want to leave the future to markets, but on the contrary to save democracy," Michael Mueller, president of the ecological organisation German Friends of Nature, told AFP.
The German government supports the trade pact, with Economy Minister Sigmar Gabriel warning of "scaremongering" in a letter published in several German newspapers.
Talks on the TTIP are due to finish next year. If agreed it would be the biggest trade deal of its kind.
Thousands have protested in the German capital Berlin against a planned free-trade deal between the EU and US.