More than 1,000 people defied a police ban as they congregated at two locations in Kuala Lumpur and marched to historic Independence Square. They held posters and caricatures of Najib, with some chanting "Catch, catch Najib."
The US Department of Justice said last month that at least USD 3.5 billion had been stolen from 1MDB, a Malaysian fund founded by Najib. It has initiated action to seize USD 1.3 billion it said was used to buy assets in the US.
Allegations against 1MDB have gained steam, but Najib has steadfastly denied any involvement or wrongdoing.
"Can we send MO1 to jail and bring that person to face justice?" student leader Anis Syafiqah Mohamad Yusof said at the rally.
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Police put barricades around the square, forcing protesters to gather around the perimeter. It was a rare protest led by student activists in the country, and backed by opposition parties and civil groups.
The state fund was created in 2009 by Najib shortly after he took office to promote economic development projects.
Instead, US prosecutors said, fund officials diverted more than USD 3.5 billion through a web of shell companies and bank accounts in Singapore, Switzerland, Luxembourg and the United States.
The money was used to pay for luxury properties in New York and California, a USD 35 million jet, and art by Vincent Van Gogh and Claude Monet, according to the DOJ complaints. It also allegedly helped finance the Hollywood film "The Wolf of Wall Street," made by Red Granite Pictures.
Najib remains firmly in political control of the country, thanks largely to the apparently unwavering support of ruling party members despite a few voices of dissent. The opposition is too weak in Malaysia to dislodge him.