Forty-eight people were killed and 90 wounded, said a hospital official in Najaf, after a car exploded a short distance away from the mausoleum of Hazrat Imam Hussain (RA).
Just two hours earlier, a car ploughed into a bus station in Karbala before exploding in a ball of fire, killing 14 people and wounding almost 50, medical sources said.
The attack happened just a short distance from the tomb of Hazrat Imam Hussain (RA).
The bombings came four days after a similar attack killed 10 people near Karbala's most revered shrine, provoking fears that insurgents trying to derail next month's key elections are increasingly targeting the Shia majority.
They were the deadliest attacks on the religious community since last March when multiple bombings in Karbala and Baghdad killed more than 170 people.
In Baghdad, three election workers were killed in an ambush around Haifa Street, a bastion of Sunni fighters bitterly opposed to the January 30 polls.
But electoral commission spokesman Farid Ayar voiced defiance, vowing that the vote would go ahead however many of his staff the "terrorists" killed.
"It's not by killing employees that the elections are going to be hindered, but the terrorists have their own strategy," he said.
One insurgent was killed and two others escaped when fighting broke out following the killings, the commission said.
Insurgents meanwhile released video footage of 10 handcuffed and blindfold Iraqis they said were employees of a US security company.
An accompanying statement threatened to kill the captives unless their employer halted its Iraq operations but gave no deadline, said the Arabic-language news channel Al-Jazeera, which aired the tape.
One of the hostages appeared injured and in pain.
Dubai-based Al-Arabiya news channel aired footage showing one of the abductors reading a statement saying the 10 hostages work for a Washington-based American security and reconstruction firm which employs 7,000 Iraqis across the country.
Faced with growing accusations by Iraqi and US officials that Damascus is stoking the Iraq insurgency, a Syrian state newspaper denied that it had "such big influence in Iraq".
"It is regrettable that Iraqi officials echo the accusations of the occupation forces (Americans), when they know very well that the Syrian-Iraqi border is under American surveillance," ran an editorial in Ath-Thawra.
"Does Syria really have such a big influence on the ground in Iraq? Is it really behind the deteriorating security in this country?"
Meanwhile, two Egyptian telecom employees working in Iraq and accused of links to anti-US insurgents were released after being arrested earlier this week.
The two were arrested "following a false tip that they were co-operating with the insurgents to block mobile phone relays," said their employer, Iraqna.
"We had them show that it was false and that for example in Fallujah and Ramadi, it was the coalition forces that had blocked transmissions," the company said.
MAJOR BOMB ATTACKS:
HERE ARE THE MAJOR BOMB ATTACKS IN IRAQ IN 2004:
February 1 - 117 people are killed and 133 wounded when two suicide bombers blow themselves in Arbil up at the offices of the two main Kurdish factions in northern Iraq.
February 10 - Suicide car bomb rips through a police station in Iskandariya south of Baghdad, killing 53.
February 11 - Suicide car bomb explodes at an Iraqi army recruitment centre in Baghdad, killing 47.
March 2 - 171 people are killed in twin attacks, which involved three suicide bombers in Baghdad and a suicide bomber, hidden explosives and mortars in Karbala. Nearly 400 people were wounded in the blasts on the day Iraqis marked Ashura.
April 21 - Suicide bombers kill 73 people, including 17 children, in co-ordinated strikes in blasts at three police stations in Basra, and at the police academy in nearby Zubeir. 94 people are wounded.
June 24 - Rebels wreak havoc in Baquba, Fallujah, Ramadi, Mosul and Baghdad with co-ordinated car bombings and assaults on local security forces in which at least 85 people, including three US soldiers, were killed and 320 wounded.
July 28 - A suicide car bomb kills at least 68 people in the Iraqi town of Baquba, including men lined up outside a police-recruiting centre.
September 14 - A car bomb near a police station in Baghdad kills at least 47 people and wounds 114 in a nearby market.
September 30 - Insurgents detonate three car bombs near a US military convoy in southern Baghdad, killing 41 people 34 of them children, and wounding 139.
December 19 - A suicide car bomb blast in Najaf, 300 yards from the Imam Ali shrine, near crowds of people, kills at least 48 and wounds 90. On the same day a car bomb explodes in Karbala, killing 12 and injuring 34, in the second such attack five days.