EU MPs gave her a standing ovation after she made the proposal and then walked over to embrace Canadian Prime Minister Mark Carney, who was in the European Parliament in Strasbourg to hear her address.
"I said we must urgently re-imagine our partnerships. So, I would like to work with you on opening the door for Canada to be the first associate member of the EU," von der Leyen said on Wednesday.
The EU and Canada "see the world with the same eyes: from AI to climate change, from the Arctic to geopolitics. And we have stood together: on Ukraine, on defence, on raw materials and on supply chains," von der Leyen told the assembly.
"But above all ... Europe and Canada believe in democracy."
New partnerships were needed "in the cold fragility of today's world", she said.
The 27-nation bloc faces war at its borders, with Russia's invasion of Ukraine.
On trade and other issues, it is also facing stiff rivalry from the administration of US President Donald Trump and from an increasingly assertive China.
The EU faces major headwinds at home as well, including the increasing popularity of a eurosceptic far right.
It will be up to EU member states whether von der Leyen's proposal goes ahead, with the EU historically resisting such types of flexible alliances that have no legal status.
EU members were lukewarm in reacting to Germany's proposal in May of associate membership for Ukraine as a stepping stone to full accession.
One EU diplomat expressed surprise at von der Leyen's proposal on Wednesday, saying "nobody really knows what it means".
The diplomat said there were concerns that the European Commission chief "is over-promising and won't be able to deliver".
And significant obstacles remain to ramping up trade.
Mark Manger, a professor of political economy and global affairs at the University of Toronto, said EU officials have been frustrated by Canada's refusal to open two industries it protects at great expense: telecommunications and dairy.
Canada's Carney was warmly applauded by EU MPs as he arrived in parliament.
He said that this week Canada was seeking a "unique alliance" with the EU but not membership.
He will make his own address to the European Parliament in France on Thursday.
Carney's European trip follows a historic breakdown in Canada-US relations after trade talks collapsed in August, sparking a series of tit-for-tat tariff measures.
He has pledged to double Canada's non-US trade in the next decade as the country pivots away from its southern neighbour amid an increasingly acrimonious trade war.
Carney said on Tuesday more detailed discussions would begin at the Canada-EU summit in Montreal in late October.
"Our relationship with the EU has become increasingly close, especially over the past year and a half," Canadian Foreign Minister Anita Anand told Reuters.
In her speech on Wednesday, von der Leyen said the EU and Canada would work together across sectors.
"We will work on intelligent manufacturing. We will create a tech alliance. We will integrate defence industrial bases. We will make the Arctic a flagship joint project," she said.
"Partnerships are a strategic choice for Europe. But they also respond to the fracture in the international rules-based system."
Von der Leyen added, "This is a partnership not against anyone else."
Turning to trade, von der Leyen said the EU would use every possible means to reduce its "unsustainable" trade deficit with China.
Von der Leyen also said the bloc would need to stay its ambitious course on mitigating climate change but also step up efforts to adapt to it, drawing on experiences from the past three months when the continent was hit by unprecedented heat waves and wildfires.
