It is believed to be the first time ever that a Vietnamese prime minister has been publicly urged to resign by a member of the one-party state's 500-strong National Assembly.
"It's time to take real responsibility not just apologise," lawmaker Duong Trung Quoc said as Prime Minister, Nguyen Tan Dung, looked on calmly.
Mr Quoc, an outspoken historian and one of the less than 10 percent of lawmakers who do not belong to the Communist Party, urged Mr Dung to "start the government's progress towards a resignation culture".
"The people are asking why it seems the prime minister does not value his responsibilities to the people as highly as he does those to the party," he said.
Mr Quoc's comments attracted an outpouring of support on Vietnamese-language online forums and blogs, which are hugely popular in the heavily-censored country, where the communist party tightly restricts political debate.
A second lawmaker, Nguyen Ba Thuyen, said Mr Dung's failure to set out a plan to overcome the country's economic woes had damaged public trust in the Communist leadership.
The growing pressure comes as Vietnam grapples with slowing economic growth, resurgent inflation, falling foreign direct investment and rising fears about toxic debts in the fragile banking system.
Mr Dung, 62, escaped punishment at a key Communist Party meeting last month over a string of scandals that have tainted the country's leadership.
But in an attempt to deflect increasing criticism, the party issued a rare self-rebuke and Mr Dung apologised for corruption, inefficiencies and major losses at state-run giants such as shipbuilder Vinashin.
Responding to Wednesday's rare public attack, a cheerful-looking Mr Dung said that he had never sought high office for himself.
"The party assigned me to continue to be the prime minister," he said, adding that he had been a loyal party member for 51 years.
"I did not lobby, I did not ask for, nor refuse, any assignment given by the party and state," he said.
The National Assembly is currently considering a resolution that could force senior leaders to win a vote of confidence to remain in office, but it is unclear whether the vote would be anything more than symbolic.
Mr Dung, a former central bank governor whose second five-year term was approved by the communist-controlled parliament in July 2011, is said to have become the country's most powerful prime minister ever.
The National Assembly, however, has also gradually become more outspoken.
In 2010 a lawmaker called in vain for Dung to face a confidence vote after the near-collapse of Vinashin.
The lawmaker's attack on Dung highlights rising dissatisfaction in Vietnamese society over the political dominance of the Communist Party, according to one Hanoi-based analyst.
"What is good for the party is not necessarily good for the people," he said.
"(Quoc's) question raises a key issue: is the supreme leadership of the party good for the country? And is it the only correct choice?"