The annual talkfest has taken on new urgency this year amid strained relations over the Iraq war.
The European Union delegation includes Greek Prime Minister Constantine Simitis, whose country holds the current EU presidency; Romano Prodi, president of the European Commission; and foreign policy coordinator Javier Solana.
They will meet with President Bush, Vice President Dick Cheney, national security adviser Condoleezza Rice, Secretary of State Colin Powell and other Cabinet members.
For years, the yearly meeting has attracted little attention on either side of the Atlantic. This time relations are at a historic low because of differences over the Iraq war and what Europeans see as Washington's disregard for allies' views.
Also in the background are disputes over trade, the International Criminal Court and genetically modified food.
There is new impetus to pull together. The European Union and the United States, along with Russia and the United Nations, jointly drafted the "road map" that they hope will lead to Middle East peace.
Greek government spokesman Christos Protopapas said the Europeans hope the summit "will constitute the starting point for a new era in the strategic partnership between the United States and Europe after the tension that existed in recent months."
The Europeans come prepared to sign an extradition and mutual assistance agreement with the United States covering terrorism and organized crime.
The EU delegation will also tell the Americans that Europe now considers weapons of mass destruction a major global threat — something U.S. officials had complained the Europeans were not taking seriously.
Both the United States and the EU have agreed to pressure Iran to agree to enhanced inspections by the International Atomic Energy Agency to ensure that Tehran does not build nuclear weapons.
On the Middle East, the Europeans are anxious to work with Washington on pursuing the "road map" to peace between Israel and the Palestinians. EU trade commissioner Pascal Lamy promised Tuesday that Europe will not use trade to pressure Israel — something the United States has been keen to hear.
Nevertheless, numerous issues divide the United States and the Europeans, in part because of wide differences in cultural, political and social views.
On a continent where coalition governments are the norm, politicians put great stock in compromise and deal-making. What Americans consider a firm stand, many Europeans sometimes see as arrogance.
France and Portugal went along with the extradition agreement only after the United States agreed that it would not seek the death penalty for suspects extradited under the treaty.
Despite broad agreement on major issues, fine print often stands in the way. The EU agreed last week to work to combat weapons of mass destruction but still insists that any military action be approved by the U.N. Security Council.
As part of the war on terrorism, the United States wants airlines flying to U.S. points to submit passenger information on request. Many European countries have strict data protection laws, enacted as a response to abuse of such information by fascist and communist dictatorships.
Other pitfalls remain.
Europe has stuck by its 1998 moratorium on the import of genetically modified foods because many European consumers fear health risks. Mr. Bush has scolded them for that stand in recent weeks, charging that it is worsening famine in Africa by discouraging African nations from investing in biotechnology.
The moratorium costs American farmers an estimated $300 million a year in lost corn exports alone. The United States plans to take the dispute to the World Trade Organization (WTO).
On Tuesday, the EU rejected Mr. Bush's complaint and claimed the EU spends seven times more on development aid to Africa than the United States.
"It is false we are anti-biotechnology or anti-developing countries," said EU spokesman Gerassimos Thomas. "These things said by the United States are simply not true."
The EU is also irked by U.S. efforts to secure bilateral agreements in which countries promise not to hand U.S troops over to the International Criminal Court, a war crimes tribunal that the Bush administration refuses to join because of fears Americans would become political targets. EU officials are annoyed by bids the U.S. has made to eastern European countries soon to join the union, according to published reports.
A number of trade disputes have also erupted. Earlier this year, the WTO ruled U.S. tax benefits for corporations operating abroad are illegal and gave approval for the EU to impose as much as $4 billion in sanctions on U.S. imports in retaliation. The EU is also fighting to overturn the Bush administration's wide-ranging tariffs on imported steel.