Waving the red flags of the CGIL union, students and young people from all over Italy led the first of four corteges to snake across the Italian capital, calling for the premier to do more to boost employment and protect the rights of new entries to the job market.
Red balloons bobbed in the sunshine above the crowds, with protesters letting off red flares in front of the Colosseum to say 'no' to the so-called "Jobs Act".
"We have no intention of giving up. Renzi must know that to change the country, he needs us, those here in the streets of Rome today," said Maurizio Landini, head of the FIOM union, which joined the CGIL protest.
Youth unemployment in the eurozone's third largest economy stands at a record 44.2 percent and those who do manage to find work are often employed on temporary contracts which offer little in the way of security or benefits.
"We are here to declare that job insecurity is not our destiny. We want investments in the future," a young person shouted through a megaphone in the crowds, while another held up a banner with a sarcastic "thanks for the 'solution' to our problems Renzi", and a picture of someone vomiting.
Renzi's centre-left Democratic Party (PD) is split over the proposed measures, with the deepest division caused by a debate over the future of Article 18, a law which currently protects those who are unfairly dismissed.
In his bid to reboot Italy's economy and lure in foreign investors, Renzi wants to make it easier for companies to fire people and introduce a system by which job protection and benefits are earned by workers over time.
But unions and many on the left are furious over the mooted changes and he has been accused of being a Thatcherite.
While the 39-year old was in Florence on Saturday addressing the "Leopolda" -- an annual meeting he founded in 2009 to bring leaders and the public together to talk about the future of Italy -- rebels from the PD were expected to join the protests in Rome.
While Italians are quick to take to the streets to protest, this is the first large demonstration by unions against the PD, with which they have historic ties.