On the second day of a European farewell tour, Obama will build on a topic he outlined on Tuesday -- the "frustration and anger" of an electorate that feels it has been left behind by rapid globalisation.
"The lesson I draw -- and I think people can draw a lot of lessons but maybe one that cuts across countries -- is we have to deal with issues like inequality," said Obama.
The 55-year-old Obama has chosen the "cradle of democracy" Greece to deliver a speech addressing the uncertainties that have led to the rise of populists like Trump.
Trump was able to tap into "a suspicion of globalisation, a desire to rein in its excesses, a suspicion of elites and governing institutions," Obama noted.
Obama's visit to Europe -- his last foreign trip as American leader -- has been all about reassuring traditional allies worried about Trump's campaign rhetoric.
Trump welcomed Britain's shock vote in June to leave the European Union and has cast doubts on the NATO alliance that has guaranteed relative peace on the continent for decades.
However, Obama was at pains to stress that Europe -- and NATO -- would remain the cornerstone of US foreign policy.
The US-led NATO grouping is "absolutely vital" to US interests and a strong, unified Europe was good for America and the world, Obama said in comments aimed at reassuring old partners.
"We know what happens when Europeans start dividing themselves up... the 20th century was a bloodbath," he said pointedly.
Obama was expected to visit the Acropolis ahead of his much-anticipated speech before heading to Germany to visit Chancellor Angela Merkel, whom he has described as "probably ... my closest international partner these last eight years".
During his time in Berlin, he will also huddle with the leaders of Britain, France and Italy, as European leaders desperately seek clues to future US policy in a Trump world.
While Obama has generally been welcomed in Greece, some demonstrators hit the streets to protest against his visit.
Some 2,500 people brandishing banners denouncing US "imperialism" and calling Obama "non grata", or not welcome, were turned away by police firing tear gas and stun grenades as they tried to breach barriers and head toward the city centre.
Many Greeks are suspicious of the United States after it helped install a repressive seven-year dictatorship in the country in the 1960s, and trade unions, leftist and anarchist parties denounce US involvement in wars in the Middle East.
Several hundred of the protesters appeared to be from Greece's vocal anarchist movement, police told AFP.
He lauded the Greek people's "extraordinary compassion" to hundreds of thousands of people arriving during Europe's worst migrant crisis since World War II.
He also pledged support for Greece's economy, as Greek leaders seek a fresh US pledge to help alleviate the country's enormous public debt, a measure actively sought by the International Monetary Fund but opposed by leading European lender Germany.
"In my message to the rest of Europe I will continue to emphasise our view that austerity alone cannot deliver prosperity," Obama told Greek Prime Minister Alexis Tsipras.