Sabri, 45, and an associate were travelling in a car in Karachi's congested Liquatabad 10 area when two unidentified motorcycle-borne gunmen fired at their vehicle, critically injuring them.
"Two attackers riding a motorcycle intercepted his car and targeted Amjad Sabri, who was driving," said Sindh police chief Allah Dino Khawaja.
The two were rushed to Abbasi Shaheed hospital, where Sabri succumbed to his injuries. His associate also died.
Additional police surgeon Dr Rohina Hasan confirmed Sabri's death. He was shot thrice - twice in the head and once on the ear.
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"Two riders used 30-bore pistols to shoot Sabri five times, the bullet to the head took the qawwal's life," a senior police official said.
There was no immediate claim of responsibility but a senior police official said, "It was a targeted killing and an act of terrorism."
Police officials recovered five 30-bore casings from the scene of the attack, which have been sent for forensics.
Both front side windows were shattered and three bullet holes could be seen on the front screen.
Amjad Sabri was the son of renowned Qawwal Ghulam Farid Sabri whose family is famous in the subcontinent for their contribution to this sufi art and mystic poetry.
Sabri was one of Pakistan's finest qawwals, known for his soul-stirring renditions of mystic poetry.
Some of the most memorable and famous qawwalis of the Sabris were 'Bhar Do Jholi Meri', 'Tajdar-i-Haram' and 'Mera Koi Nahin Hai Teray Siwa'.
Prime Minister Nawaz Sharif has condemned the attack and has directed authorities to bring the perpetrators to justice.
Fakhre Alam, Chairman of Sindh Censor Board, has claimed in a tweet that Sabri had earlier submitted an application for security, but the home department did not act on it.
His killing comes just two days after the son of the Sindh High Court Chief Justice was kidnapped and it raises serious concern about the security situation in Pakistan's biggest city. This week a doctor belonging to the minority Ahmadi community was also shot dead in his clinic by gunmen.