Militants attacked a police compound in the heart of Pakistan's largest city with a hail of gunfire and massive car bomb, levelling the building and killing at least 15 people.
The gang of around six gunmen managed to penetrate a high-security area of Karachi that is home to the US Consulate, two luxury hotels and the offices of regional leaders.
Sindh government spokesman Sharmila Farooqi said 15 people, including five police officers, were killed. About 100 people were injured.
It was the first major attack against a government target outside the north west tribal regions for several months, showing the reach of Islamist militants seeking to overthrow the US-allied government despite efforts to crack down on them over the last three years.
The gunmen first opened fire on the offices of the Crime Investigation Department (CID) before detonating a huge car bomb, said Sindh home minister Zulfiqar Mirza. The building has a detention facility that was believed to be holding arrested people and possibly militants.
The CID takes the lead in hunting down terrorists in Karachi. Earlier this week, the agency arrested six members of Lashkar-e-Jhangvi, an al-Qaida linked group blamed for several high profile attacks in recent years. The suspects were in court earlier on Thursday.
The blast could be heard several miles away in the city of 14 million people. It destroyed much of the multi-storey police building, damaged nearby houses and left a 10ft crater in the road. The US Consulate is around a mile away and was undamaged.
"We heard different kinds of firing for several minutes and then a deafening explosion," said Ali Hussain, who was covered in dust. "The roof of our house collapsed."
Bloodied and dazed victims were taken to ambulances, some of them children pulled from the debris.