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After 18 years at the head of the Christian Democratic Union (CDU), Merkel had to face an "uprising" when deputies removed their right arm.
The decision, which saw parliamentary leader Volker Kauder ousted and replaced by Ralph Brinkhaus, highlighted the fragility of the Chancellor as she clings to power.
A CDU adviser told the Financial Times that "Kauder was the first domino to fall, but there could be more.
"It could be just the beginning.
"I can imagine that all the top party leadership is under pressure to resign, including Merkel."
MEPs also called the decision "an uprising against Merkel".
Time is running out for the Berlin boss as he faces calls to resign from his 13-year-old German prime minister, Bild, who asked: "Can Merkel still be Chancellor?
EU Budget Commissioner Günther Oettinger, also a key member of Angela Merkel's CDU, said: "It's normal, it's a lame duck."
Oettinger told political news site Politico.co.uk that the decision had "weakened the Chancellor", but that did not mean the end of the Merkel era.
Merkel had appointed Mr. Kauder, an arch-loyalist who served as his parliamentary leader for 13 years for re-election, and his choice was approved by the rest of the party leadership.
But Mr. Kauder, 69, was beaten by Mr. Brinkhaus, an unknown parent who said he ran as a candidate to renew the party.
The popularity of Angela Merkel was undermined after her open door policy saw more than one million African and Middle Eastern refugees arrive in Germany in 2015.
After heavy losses in last year's elections, Merkel faced the biggest threat to her power this summer when Horst Seehofer, her minister of the interior and leader of the Christian Social Union (CSU) ), threatened to close the German borders to migrants.
The German leader was forced to turn a corner when Mr Seehofer threatened to defy his wishes and ordered the police to fend off the asylum seekers unless she reached a wider agreement with the police. EU on the fairer distribution of migrants.
This decision could have forced Merkel to sack him, causing the collapse of his three-month government, as well as the Schengen free movement area.
