A mortar attack targeted a huge gathering around the main mosque on Kufa on Thursday.
The second struck at thousands marching towards Najaf, where resistance fighters loyal to Shia leader Muqtada al-Sadr have been defying US-led occupation forces in a bloody standoff.
It was not clear who mounted the attack on the Iraqis in Kufa, who included supporters of al-Sadr and of senior Shia spiritual leader Ayat Allah Ali al-Sistani.
Soon after, thousands of demonstrators from Kufa loyal to al-Sadr and al-Sistani marched on nearby Najaf, but came under fire from a base between the two cities housing Iraqi national guardsmen and US troops, witnesses said.
In the past, al-Sadr has regularly used the Kufa mosque to deliver sermons at Friday prayers.
The marchers scattered when the gunfire broke out. Casualties were carried away in private civilian vehicles and ambulances.
Vehicles have rushed wounded to
the nearest medical facilities
"The Najaf hospital received 39 bodies and 255 wounded and the one in Kufa 25 bodies and 60 wounded," a health ministry official said.
The bodies of another eight people killed in the demonstration and 42 wounded people were transported to Diwaniya, about 50 kilometres east of Najaf.
Two other bodies and 19 wounded were taken to a hospital in Hilla, about 60 kilometres north of Najaf.
"We cannot distinguish between those who died in the bombing of the Kufa mosque and those who were killed in the demonstration," he said.
Earlier, the gathering at the Kufa main mosque was in response to al-Sistani's call to Iraqis to head to the besieged Imam Ali shrine.
"We were gathering outside and inside the mosque preparing to head to Najaf when two mortar shells landed, one inside the mosque and the other on the main gate," said Hani Hashim, bringing an injured friend to the hospital.
"This is a criminal act. We just wanted to launch a peaceful demonstration."
Husam al-Husaini, an aide to Shia leader Muqtada al-Sadr, said one mortar shell hit the mosque itself and two others hit near the mosque gates.
The local hospital has struggled to
accommodate all the casualties
Al-Husaini said another mosque in Kufa had also been hit by mortar rounds. It was unclear whether there were casualties there.
In other developments, informed sources told Aljazeera that Ali al-Dhabhawi, a religious consultant for the former governor of Iraqi province of Babylon and his son were assassinated on Wednesday by unidentified armed men.
On Wednesday, three mortar rounds, apparently targeting a police checkpoint, hit a civilian area in Kufa, killing two civilians, including an eight-year-old boy, and wounding four others, witnesses and hospital officials said.