"We call upon all Malaysians, irrespective of race, religion, political situation, creed or parties, young and old, to join us in saving Malaysia from the government headed by Najib Razak," read a joint statement endorsed by heavyweights from the ruling party, opposition, and top civil society groups.
The historic alliance brought together previously bitter political foes and was led by former premier Mahathir Mohamad, who has spearheaded calls to remove Najib over allegations of corruption and misrule.
"We must rid ourselves of Najib as prime minister," he said.
The move marks the greatest challenge yet to Najib, and lends a potent voice to a growing public sense of disgust with his tenure.
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Najib, 62, has been under fire for a year over allegations that billions of dollars were stolen from a state firm he founded, and his own admitted acceptance of a murky $681 million overseas "donation".
Amid cascading calls to step down, he has counterattacked by purging his ruling United Malays National Party (UMNO) of critics and shutting down investigations.
The joint statement by the anti-Najib alliance lamented the "deteriorating political, economic and social situation in the country".