Jean-Claude Juncker will say it is time for the EU to take its place at the top table of global powers.
He is also expected to predict the UK will have better relations with the EU than any other country after Brexit.
This is Mr Juncker's last 12 months in the role, with the problems of Brexit, migration and populism dominating.
The commission head will propose a new Africa-Europe alliance, based on co-operation rather than charity, leading to a continent-to-continent free trade agreement.
He will recommend that the euro be used more strategically as the biggest currency after the dollar.
And he will urge countries to give up their national vetoes in some areas of foreign policy. One EU diplomat said this would be an attempt to prevent China - a growing force in Africa - from blocking European diplomacy with a call to just one of the member states.
Although this is the final state of the union address before Brexit, our correspondent says Mr Juncker will not want the subject to dominate.
It is unlikely he will shift the EU's position towards the UK's on access to the single market - but he will nod towards a future relationship that will be unlike any the EU has with another country.
An EU diplomat said the message is: "Let's be friends again."
On migration, there will be more details on EU plans to add 10,000 guards to the Frontex border agency by 2020.
From the start of his commission's mandate in 2014, migration his been a major crisis.
It has sparked a rise in populism that has seen power shifts in Italy, Austria, Hungary and Poland, with Sweden the latest country to register a rise in anti-immigration votes in an election.
Right after his speech, the EU parliament will decide whether to take disciplinary procedures against Hungary for breaching core democratic values.
The commission has already launched disciplinary proceedings against Poland over reforms it says challenge the rule of law.
The next elections to the European parliament are expected to be held in late May next year.
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