The long-awaited summit is the first between Brussels and the Community of Latin American and Caribbean States (CELAC) since 2015, with several issues undermining closer ties.
"We need our close friends to be at our side in these uncertain times," European Commission president Ursula von der Leyen said, welcoming Brazil's President Luiz Inacio Lula da Silva.
Von der Leyen promised that Europe would invest 45 billion euros in the Latin American economy under the Global Gateway programme, Brussels' answer to China's "Belt and Road" outreach to developing economies.
As EU and CELAC leaders gathered in Brussels, diplomats were struggling to agree on the wording of the final communique -- with Europe pushing for a strong stance against Moscow.
But the 33 nations of Latin America and the Caribbean have no agreed position on the Ukraine war, and some want to protect ties with Russia or seek a compromise peace deal.
Instead some CELAC delegates will push for the implementation of the 2019 EU-Mercosur trade deal, which has stalled on European concerns about deforestation and agricultural competition.
Three years after agreeing the deal liberalising trade between the EU and Argentina, Brazil, Paraguay and Uruguay, it has yet to be ratified by several European governments.
Some capitals had hoped that the summit, held under Spain's EU presidency, would bring new momentum on the Mercosur deal.
But diplomats from both blocs were clear that no breakthrough on trade was expected at Monday's talks.
A senior Spanish diplomat told reporters in Brussels that EU-CELAC "will be a political summit, not a negotiating summit".
And Gustavo Pandiani, Argentina's undersecretary for Latin American affairs, predicted "consultations and political dialogue about broad political lines.
"We are not going to talk about tariffs," he said.
"Someone announced four years ago that we had an agreement, and now we're still discussing it. So, it's likely that we didn't have an agreement then."
The first signs of trouble for the trade deal came under Brazil's former right-wing populist government, with then-president Jair Bolsonaro unleashing a wave of agricultural development in the Amazon.
Bolsonaro -- an admirer of US President Donald Trump -- has since been replaced by leftist Lula da Silva, who has better green credentials. But Europe's relief was short-lived.
Brazil under Lula has proclaimed itself "neutral" in Russia's war against Ukraine, and has pushed back against Europe's bid to attach rules against deforestation to the Mercosur trade pact.
Speaking at the business forum, Lula did not explicitly address the issue of Ukraine, but made it clear that he thought it a distraction from Brazil's pressing issues.
"The war in the heart of Europe has launched, over the world, uncertainties. And it channels for war purposes resources that were essential for the economy and for social programs," he said.
"The arms race makes it even more difficult to confront the climate change issue."
Von der Leyen was diplomatic. "I welcome Brazil's re-emergence as a major actor on the global stage," she said.
In 2020, the EU adopted its so-called Green Deal, which was not aimed at Latin America in particular, but binds its trade deals to tougher environmental standards.
In March, the EU presented a set of proposals to update the Mercosur deal, including binding limits on deforestation, with trade consequences -- triggering Brazil's anger.
"We are back in government in order to put Brazil once again as a protagonist in the international arena," Lula said, at a brief pre-summit appearance with von der Leyen.
"We want to discuss the climate issue," he added. "The energy and climate transition is now a priority for our government."
And if the summit is unlikely to unblock the trade deal, the leaders may also struggle to find common ground on broader international issues.
Europe wants the CELAC countries to sign up to a statement supporting Ukraine and condemning Russia since the start of the 16-month-old war.
Brazil, however, has argued that Kyiv and Moscow share responsibility for the conflict, and Cuba and Venezuela have remained traditional Russian allies.
Ukraine's President Volodymyr Zelensky has addressed summits including the Arab League, the African Union and the G7 by video link -- but has been barred from EU-CELAC.
The summit is due to last two days.