Several policemen also were injured in the blast that targeted the car of Chaudhry Muhammad Aslam, chief of the crime investigation department of Sindh Police.
Aslam's car was destroyed in the late afternoon blast after a suicide bomber slammed his vehicle into Aslam's before detonating a bomb.
Only the frame of Aslam's car remained, ending upside down 65 feet from the impact.
The blast was so powerful, it destroyed two other police vehicles in the convoy and damaged nearby buildings, The Nation reported.
Aslam was known to have been on the terrorist's hit list for several years and was a target in particular after he killed three Taliban militants in a gun battle in Karachi earlier this week.
In September 2011, eight people were killed and several injured when a car packed with explosives went off outside Aslam's Karachi home, The Nation reported.
In 2010, the terrorists also blew up the head office of CID in Karachi.
The Mohmand chapter of the banned terrorist group Tehrik-i-Taliban Pakistan claimed responsibility for the attack, the newspaper Dawn.com reported.
Sajjad Mohmand, a spokesman for the militant group, said Aslam was killed for carrying out operations against the Tehrik-i-Taliban Pakistan.
"Aslam was involved in killing Taliban prisoners in CID cells in Karachi and was on the top of our hit list," he said.
Aslam was one of Pakistan's most controversial top cops.
He was praised for his dogged pursuit of terrorists, but criticized for his alleged harsh treatment of them during, and after, gun battles and police raids.
Since 2008, his unit arrested of dozens of militants, including would-be suicide bombers, planning attacks in Pakistan and across the border in Afghanistan, the BBC reported.
But Aslam often was accused of faking dramatic encounters with Taliban and suspected militants. He allegedly would capture and kill militants in staged gunfights instead of arresting them and putting them through the judicial process, the BBC reported.
He denied staging any fake encounters.
An internal police inquiry cleared him of any incidents of fake encounters.
"Chaudhry Aslam was a brave officer," Prime Minister Nawaz Sharif said. "We will not let the will of the nation be crushed by these cowardly acts by terrorists."
Aslam's wife said her husband often shrugged off threats to his life.
"He never once succumbed to threats, never talked of backing out," she told Express News.
"If he wanted to, he would have done so after the attack at our house. Instead, he would always say, 'On the day I'm destined to die, no one will be able to save me and on the day I'm not, no one could kill me.'"
She also said he wasn't in his usual bomb-proofed car because it was in for repairs this week.