Thousands marched outside the US Embassy in the Greek capital, holding up signs that read "Pompeo go home," and threw red paint on a statue of former US President Harry Truman in the city centre.
Greece and the United States have traditionally close relations even though many blame Washington for its tacit support for a military junta that ruled Greece between 1967 and 1974. Protest marches to the US Embassy are an annual event.
Demonstrators, which included supporters of the Greek Communist Party, held banners against Greek - US military cooperation. The United States uses a base on the island of Crete for naval and sea operations in the region.