"Vladimir Putin is intent on undermining democracies throughout the world, make no mistake about it. We should be very candid about that," Pompeo told journalism students in the capital Bratislava.
He later warned Slovaks about the "the need to guard against China's economic and other efforts to create dependence and manipulate your political system."
Pompeo is seeking to highlight the US role in the fall of communism three decades ago at a time when Putin finds a widening audience in the former Eastern bloc.
The first US secretary of state to visit Slovakia in 14 years, Pompeo told President Andrej Kiska: "It's been too long since America has been deeply engaged here."
He met with five former political prisoners at a memorial to the so-called Gate of Freedom on the border with Austria, where 400 people were killed from 1945 to 1989 as they tried to break through the Iron Curtain to the West.
"Where barbed wire and armed guards stood, today people, goods and information cross freely," Pompeo said.
"The United States has stood with the people of Slovakia as a friend, as a partner... for the past 30 years, and we will continue to stand with you in the decades to come.
"On behalf of the United States I'm proud to stand in union with the people of Slovakia and Europe in recommitting to a future that is more prosperous, more secure and, most of all, great," he said.
Kiska, a staunch liberal, called the US an "important partner and ally".
President Donald Trump has voiced admiration for Putin but the wider US government remains suspicious of the Russian leader and is seeking to find alternatives for European nations to Russia's energy exports.
A senior US official travelling with Pompeo said the Trump administration was pursuing a strategy similar to that in Asia, where for years the United States has been seeking to curb China's power.
"It emphasises in vulnerable regions where our rivals, the Chinese and the Russians, are gaining ground that we want to increase our diplomatic, military and cultural engagement," the official told reporters.