Renewed protests began on Thursday evening in a month of deadly unrest that has claimed more than 200 lives.
Forty-two people died in renewed anti-government protests across Iraq on Friday.
According to watchdog and security sources, half of the victims were killed while trying to storm the offices of militia groups and the government.
The protests represent the second phase of a week-long movement in early October that ended with more than 150 people dead.
Twelve people died as they set fire to the headquarters of the paramilitary force in the southern city of Diwaniyah.
According to the Iraqi Human Rights Commission, 30 others have also died, while 2,000 people across the country have reportedly been wounded throughout the month.
Some protesters could be seen exchanging flowers with security forces as the interior minister insisted police would "protect" protesters.
Most of the deaths occurred as a result of tear gas canisters that were fired directly at protesters, as well as rubber bullets and live ammunition.
Protesters also set local government headquarters ablaze in the southern Iraqi province of Dhi Qar, a police source said, as renewed anti-government rallies gripped the country.
AFP's correspondent saw columns of smoke rising from the building where several thousand protesters had gathered to demand an overhaul of the political system.
Several political party offices were also set on fire in protests elsewhere in the south, police said.
More than 30 people were taken to hospital with breathing difficulties, security officials said.
The confrontations began early in the morning after anti-government demonstrations resumed, following a three-week hiatus.
An Iraqi security source, who asked not to be named, said the police used force to disperse protesters who entered the Green Zone that houses key government buildings and foreign embassies.
Despite heavy security deployment around the Green Zone, the protesters blocked key bridges connecting the diplomatic enclave to Tahrir Square in downtown Baghdad.
"The police used water cannons to disperse the protesters," the police source told Anadolu Agency.
In the Iraqi provinces of Basra and Thi Qar, protesters gathered in public squares and in front of government buildings. They also held sit-ins.
Dozens of security men injured
The Iraqi Interior Ministry, for its part, said more than 60 members of the security forces were injured during Friday's demonstrations.
The ministry spokesman Khaled al Mehna said in a televised interview that "security forces have a duty to protect the demonstrators."
"Violence is not in anyone's interest," he asserted.
The protests began October 1 over corruption, unemployment and lack of basic services but quickly turned deadly as security forces cracked down, using live ammunition for days.
The protests then spread to several, mainly Shia-populated southern provinces and authorities imposed a curfew and shut down the internet for days in an effort to quell the unrest.
After a week of violence in the capital and the country's southern provinces, a government-appointed enquiry into the protests determined that security forces had used excessive force, killing 149 people and wounding over 3,000. Eight members of the security forces were also killed.
The protests, unprecedented in their scale, threatened to plunge Iraq into a new cycle of instability that potentially could be the most dangerous this conflict-scarred nation has faced, barely two years after declaring victory over Daesh.
Subsequently, Iraqi security forces and government officials vowed to avoid further deadly violence and deployed heavily on the streets of Baghdad in anticipation of Friday's protests.
As in the protests earlier this month, the protesters, organized on social media, started from the central Tahrir Square. The demonstrators, mostly young, unemployed men, carried Iraqi flags and chanted anti-government protests, demanding jobs, water and electricity.
'Corruption is out'
"I want my country back; I want Iraq back," said Ban Soumaydai, 50, an employee at the Iraqi Education Ministry who wore black jeans, a white T-shirt and carried an Iraqi flag with the hashtag #We want a country printed on it.
However, after thousands of protesters crossed the Jumhuriyya Bridge leading to Baghdad's heavily fortified Green Zone, home to the US Embassy and Iraqi government offices, soldiers fired at first just tear gas, then live rounds to push back the protesters after they removed concrete barriers in an effort to reach the Green Zone's entrance.
"Baghdad hurra hurra, fasad barra barra," they chanted, Arabic for "Baghdad is free, corruption is out."
Riot police in full gear and armed soldiers lined the bridge. Ambulances zipped back and forth, ferrying the injured to hospitals for treatment.
Prime Minister Adil Abdul Mahdi has struggled to deal with the protests.
He gave an address to the nation in the early hours on Friday, promising a government reshuffle next week and pledging reforms. He told protesters they have a right to peaceful demonstrations and called on security forces to protect the protests.