But never before has the German chancellor had to contend with another woman, a popular member of her own cabinet, standing up to her in public in the way Labour Minister Ursula von der Leyen did last week.
The 54-year-old von der Leyen forced Merkel to retreat on, of all things, women's rights in a riveting public showdown just five months before an election.
"It's like von der Leyen threw a stick of dynamite into the coalition," said Gero Neugebauer, political scientist at Berlin's Free University. "You have to go back to the 1970s to find a minister who stood up to a chancellor. She made Merkel look weak."
Political analysts, conservative party members and German voters are now watching to see if there will be any fallout.
Most believe that von der Leyen, who regularly polls among the most popular politicians in Germany, remains too important to Merkel and the party to dump, especially with the election looming. The showdown may burnish von der Leyen's image among some voters, even if it has infuriated conservatives in the ruling Christian Democrats (CDU).
Just one year ago, Merkel summarily fired her Environment Minister Norbert Roettgen after he bungled an important regional election. Over the past decade, she has found ways to neutralise other potential rivals, from former CDU parliamentary leader Friedrich Merz to state premiers Roland Koch, Guenther Oettinger and Christian Wulff.
Von der Leyen, a trained gynaecologist, has a history of pushing her party towards the political centre even if it means poaching ideas from the left-leaning Social Democrats (SPD).
Her popularity stems from her engaging speaking style, down-to-earth manner and the determined way in which she's pushed her issues, notably a drive to create more childcare facilities in a country of stay-at-home mothers.
Still, her threat last week to break ranks and back an opposition bill to establish quotas for women on company boards was seen as an act of betrayal in some conservative circles.
Mother of Seven
A mother of seven who was born in Brussels and lived in Britain and the United States, von der Leyen grew up surrounded by politics. Her father, Ernst Albrecht, was a CDU state premier for Lower Saxony from 1976 to 1990.
She is a rarity in German politics in that she came to the game late, when she was 42, following a career in medicine.
Von der Leyen speaks fluent English and French. She studied at the London School of Economics from 1977 to 1980, but used the pseudonym "Rose Ladson" due to concerns she might be targeted, as the daughter of a prominent politician, by left-wing guerrillas who were active in West Germany at the time.
She graduated from medical school in 1987 and worked as a physician until 1992. While raising her fast-growing family, she lived in California from 1992 to 1996 while her husband Heiko taught at Stanford University. She met him at a university choir in Goettingen.
Von der Leyen is resented by some for seeming too perfect. She was once hoisted out of a barrel on German entertainment TV by Hugh Jackman and kissed by George Clooney after handing him an award for promoting peace.
She is admired by others for her ability to juggle a demanding career and family, while skillfully representing Germany on her frequent trips abroad.
"Von der Leyen can go to Harvard or the Sorbonne and give big speeches in English and French," said Markus Kerber, managing director of the BDI industry association, who knows her well. "For me she represents a new generation of Germans who can communicate internationally."
In 2003 she was elected to the Lower Saxony state assembly and in 2005 Merkel picked her as her family minister.
Von der Leyen quickly made it clear she was not going to be a token mum in the cabinet - Merkel and then-Education Minister Annette Schavan had no children.
In a bid to counter Germany's low birth rate, she co-opted an SPD proposal to introduce paid parental leave for working parents, a move which angered party conservatives.
She has tried to change German attitudes towards children, clouded as they are by the Nazi campaign to encourage procreation.
"In the United States people would say 'Oh, seven children, you are so blessed," von der Leyen told Reuters in 2005. But in Germany the reaction was: "Seven children and a job - how are you going to manage that?"
How does she manage it?
Good planning is the key, she says. Unlike many other German politicians, she is rarely seen socialising in Berlin, preferring instead to spend weekends at home in Lower Saxony with her family.
She doesn't have a flat in the German capital, instead sleeping in a small ministry room with a bed and shower.
Many men have learned the hard way not to underestimate Merkel. The same may be said for von der Leyen, who stands just 1.61 meters tall (5 foot 3 inches).
In the recent standoff over female quotas, Merkel deputies, led by parliamentary floor leader Volker Kauder, managed to pressure von der Leyen to back down. But only after she and her fellow rebels extracted from the party a promise to include a quota in its election programme.
"Von der Leyen showed in this debate that she is ready to fight for what she wants," one close ally of Merkel said. "But she also showed that she doesn't understand her party, that she isn't on the same page as the majority of her CDU colleagues."
Still, political scientist Hans Vorlaender of the Technical University in Dresden, says it would be wrong to count von der Leyen out.
"The CDU is a party that is above all interested in staying in power," he said. "If after Merkel is gone it turns out von der Leyen is seen as their best option to win power, she'll be their candidate."