Wielding red flags and placards, they urged the centre-left Prime Minister, Enrico Letta, to scrap austerity measures and focus on job creation.
Public trust in his fragile coalition with the centre-right is dropping, opinion polls suggest.
The country is experiencing its longest recession in more than 40 years.
National debt is now about 127% of annual economic output, second only to Greece in the eurozone.
Unemployment is at a record high of 11.5% – 38% for the under-25s.
The issues of social justice and poverty came up when German Chancellor Angela Merkel had talks with the new Pope at the Vatican on Saturday.
Organised by the metalworkers’ union FIOM and the CGIL union, Saturday’s peaceful march and rally drew supporters from across the country.
“We ask the government to change [former Prime Minister Mario] Monti’s and [former Prime Minister Mario Silvio] Berlusconi’s politics,” said Maurizio Landini, leader of the FIOM.
“If they don’t change, as the country asked for with its vote, we are going nowhere.”
One of the protesters, Enzo Bernardis, told Reuters news agency: “We hope that this government will finally start listening to us because we are losing our patience.”
Soon after being appointed, Mr Letta met other eurozone leaders to convey growing public unrest over austerity measures in Italy.
But the new prime minister has to maintain a delicate balance between the policies of his own supporters and those of the centre-right, led by Mr Berlusconi.
Italy’s coalition was only formed after two months of post-election deadlock.
A controversial poster depicted Chancellor Merkel, who is seen as typifying austerity, in mock-Nazi uniform.
On Thursday, the Pope said in a speech that the global economic crisis had made life worse for millions in rich and poor countries.
Speaking after her private meeting with the pontiff, Mrs Merkel told reporters: “Crises have blown up because the rules of the social market have not been observed… It is true that economies are there to serve people and that has by no means always been the case in recent years.”
Mrs Merkel said she and Pope Francis had spoken mainly about globalisation, the European Union and the role of Europe in the world.
“Pope Francis made it clear that we need a strong, fair Europe and I found the message very encouraging,” she added.
While she is not a Catholic herself, Mrs Merkel, the daughter of a Lutheran minister, leads a party with a strong Catholic component.