In an open letter to leaders of the 27 member states, Tusk included the Trump administration as part of a group of 'dangerous' challenges facing the EU, citing Russia, China and radical Islam as other threats.
"The change in Washington puts the European Union in a difficult situation, with the new administration seeming to put into question the last 70 years of American foreign policy," Tusk said.
He issued a call for 'political solidarity' before a summit in Malta later this week where Europe's heads of states will gather to discuss the future of the bloc, the Independent reported on Tuesday.
The former Polish prime minister said that an assertive China, Russia's aggressive policy, 'terror and anarchy' in the Middle East and 'worrying declarations by the new American administration' put the future of Europe in jeopardy.
"The disintegration of the European Union will not lead to the restoration of some mythical, full sovereignty of its member states, but to their real and factual dependence on the great superpowers: the US, Russia and China."
Trump had earlier called Nato 'obsolete' and dismissed the 28-member EU as a 'vehicle for Germany' and said he's had 'a very bad experience' with the EU as a businessman, said a report in CNN.
Stefan Lehne, a former EU diplomat from Austria, said Tusk's "dramatic language is something you wouldn't expect. It's extremely worrying, but I can see why. Trump's policies to the EU are completely unprecedented."
"Every Brit and European was socialised to expect the US to lead on every international crisis. Now you have a US President who wouldn't mind at all if the EU fell apart," CNN quoted Lehne as saying.
Tusk's statement comes as the EU faces Russian assertiveness, a refugee crisis, rising populist movements in Europe and critical elections in France, the Netherlands and possibly Italy.