The mosque was packed for Friday afternoon prayers when it was shattered by the fourth and worst bomb attack in five days in Pakistan, a frontline state in the US-led war on terror.
President Pervez Musharraf called the attack a "heinous act of terrorism" and ordered an immediate inquiry.
Angry Shia went on a rampage in central Karachi, pelting cars and shops with stones and setting fire to a state-run petrol station, several vehicles, a building and a police post
near the mausoleum of Pakistan's founder Muhammad Ali Jinnah.
Karachi police chief Tariq Jameel said 15 people were killed in the mosque bombing. Officials said another 125 were wounded.
"It appears to be a suicide attack," said provincial security adviser Aftab Sheikh. "The explosives were attached to the body of the bomber who was apparently in the third row of worshippers."
'Blood and bodies'
An employee of a brokerage house said he heard two consecutive explosions. "Our office on the 14th floor was shaken," he said. "We saw plumes of smoke, blood and bodies."
It was just the latest in a series of attacks on Shia mosques in Pakistan, which has long been troubled by violence between the minority Islamic sect and armed majority Sunnis.
Earlier, three people were wounded in the southwestern city of Quetta, capital of Baluchistan province, when a small bomb exploded opposite a hotel that is scheduled to play host to a weekend investment conference.
Prime Minister Zafarullah Khan Jamali had been expected at the city's Serena Hotel on Saturday to chair the conference.
However, Jamali had cancelled his plans to attend the conference before the blast due to party commitments in Islamabad, said Information Minister Shaikh Rashid Ahmad.
The chief minister of Baluchistan, Jam Mir Mohammad Yusuf, called the blast an attempt to sabotage the meeting.
Quetta police chief Qazi Wahid said the blast was caused by a small time bomb attached to a bicycle.
"Our office on the 14th floor was shaken. We saw plumes of smoke, blood and bodies"
An employee of a brokerage house
Baluchistan is one of Pakistan's poorest regions and has been frequently troubled by Islamic armed fighting and tribal violence.
On Thursday, another small bomb exploded outside the ticket office of Quetta railway station, but caused no injuries.
And on Monday, a car bomb exploded in the fishing town of Gawadar in the far south of Baluchistan, killing three Chinese technicians working on a project to build an major port.
Police have detained 17 people in connection with that attack, which officials blamed on "terrorists", but have yet to make a formal arrest.