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The bus station was very busy at the time of the attack
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The attacker detonated explosives at a crowded bus station in the city close to a shrine holy to Shia Muslims, at around 0915 local time (0515 GMT).
Many of the casualties were said to be women or children.
Meanwhile in Baghdad at least 10 people died in a truck bomb attack on a key bridge in the south of the city.
The driver of the pick-up detonated his bomb near a checkpoint on the Jadariya bridge, across the River Tigris. The bridge appears to have been left intact.
This follows a truck bomb which partially destroyed the Sarafiya bridge in northern Baghdad on Thursday, killing eight people.
The attacks come as a US-led security operation enters its third month.
The surge has brought down the rate of sectarian murders in the capital but has failed to stop bomb attacks.
Correspondents say the latest attacks suggest a change in tactics by insurgents, who are targeting infrastructure in an attempt to undermine confidence in the crackdown.
Ambulances
In Karbala, witnesses said police fired into the air to disperse crowds and clear the roads near the bus station, which had been particularly busy at the time of the attack.
Iraqi television aired footage in which rescue workers could be seen evacuating casualties. As many as 15 ambulances were said to be at the scene.
Karbala's director of health told the BBC that 36 people were known to have been killed in the attack.
Another 168 people had been hurt, of whom around 15 were very seriously injured, he said. Earlier reports from the Iraqi military and hospital officials had suggested the number of deaths was higher.
Hundreds of people were seen gathered around the ambulances and pounding their chests in grief.
"What did they do to deserve this," a woman searching a hospital for her daughter and grandson told the Associated Press news agency.
"To whom should I complain? There is no government to protect us," she said.
Curfew
Demonstrations followed outside the Karbala governor's offices.
Protesters threw stones at the offices, demanding the resignation of the governor and provincial council members and blaming them for security lapses.
Police imposed a curfew and sealed off entrances to the city.
The attack occurred about 200m from the Imam Hussein shrine, where the grandson of Islam's Prophet Muhammad is believed to be buried.
The BBC's Jim Muir in Baghdad says the location of the attack, plus the fact that it was clearly aimed at Shia Muslims, makes it highly provocative.
Karbala, which is 80km south of Baghdad, is the destination of a Shia pilgrimage every March.
More than 100 people were killed during last month's pilgrimage.