The first woman to hold the top EU post, von der Leyen has come to embody an institution long cast as faceless, projecting renewed European assertiveness on the world stage.
But her bulldozing dynamism has at times put her at odds with EU capitals.
The 65-year-old German conservative is walking a tightrope as the flagship achievement of her first term -- the European "Green Deal" -- turns politically toxic, under fire from farmers who have been staging protests and part of her own camp.
Reading the shifting public mood, von der Leyen has pivoted from climate concerns since announcing her bid last month, positioning herself instead as champion of a hawkish new European security outlook.
"The threat of war may not be imminent, but it is not impossible," she told European lawmakers in a sombre address that spoke of "shattered" illusions and the need for the EU to "wake up" to a perilous new security reality.
During her first term the commission chief worked to expand the bloc's international role, and also pushed -- overstepped, her critics would say -- the boundaries of her own job.
She has on occasion infuriated EU leaders, like last October, when while visiting Tel Aviv she backed Israel's right to defend itself against Hamas, without stressing that any military response must be bound by international law.
- 'Made her mark' -
Von der Leyen was a relative unknown outside Germany when she was tapped for the top EU job in 2019, in a surprise deal between Paris and Berlin.
When first appointed, the welcome in Brussels -- the city where she was born and lived until her early teens -- was cool to say the least. She secured the European Parliament's backing by just nine votes.
"VDL," as she is nicknamed in EU circles, still has her detractors.
Operating from the 13th floor of the Berlaymont, the commission's hulking headquarters where she also has her sleeping quarters, she relies on a tight-knit coterie of advisors -- a practice that rubs many the wrong way.
But von der Leyen has made her mark in Brussels.
"There were a couple of major inflexion points where she managed to do the things that were needed and made herself visible doing them," summed up one European diplomat.
When Europe was brought to its knees by the Covid-19 pandemic, von der Leyen steered a groundbreaking 750-billion-euro ($815 million) recovery plan.
After Russia invaded Ukraine in February 2022, she was resolute in her support for Kyiv, setting to work on reducing Europe's energy dependency on Moscow.
- Biden 'trusts her' -
Beyond the bloc's borders, she has provided -- to some extent -- an answer to the old question attributed to Henry Kissinger: when the US president needs to speak to Europe, who does he call?
For Ian Bremmer, founder of the Eurasia Group risk consultancy, von der Leyen built a "very good" relationship with President Joe Biden.
"Biden trusts her, he likes her," Bremmer told AFP. "They coordinate well."
Though the mother of seven has long championed women's rights, von der Leyen's gender has seldom been an issue in office -- save for an infamous incident known as Sofagate.
During a visit to Istanbul in April 2021, the commission chief found herself relegated to a sofa during a meeting with President Recep Tayyip Erdogan and Charles Michel, her European Council counterpart, when both men took seats in a pair of armchairs.
The scene went viral, and von der Leyen pulled no punches afterward, telling lawmakers: "I have to conclude, it happened because I am a woman."
Von der Leyen started out in local German politics in the 1990s, kickstarting a rapid rise: she was once viewed as a presumptive successor to Angela Merkel until her star dimmed at home following a rocky stint as defence minister.
Three months from European elections that will reshuffle the political cards in Brussels, von der Leyen -- while by no means a shoo-in for a second term -- is seen as having a strong shot.
But even if the European People's Party (EPP), which will formally tap her as its candidate Thursday in Bucharest, remains the biggest force in parliament, the choice of a commission chief is famously subject to horse-trading among EU capitals.
That can be an unpredictable process, as shown back in 2019 with the surprise appointment of a low-profile German politician named... Ursula von der Leyen.
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