Officials said the attack hit the vehicle of Quetta's Deputy Inspector General of Police Hamid Shakil during his morning commute in the provincial capital.
"Hamid Shakil, his driver and an assistant sub-inspector were martyred when a suspected suicide bomber struck his motorcycle with his vehicle," senior police official Naseeb Ullah told AFP.
Four other policemen were also wounded in the bombing, the officer said, adding that Shakil was wounded in the blast but died en route to hospital.
Commissioner Quetta Amjad Ali Khan confirmed the attack and said that according to initial reports it was a suicide bombing, but he would wait for investigators to follow up on the nature of the incident.
There were no immediate claims of responsibility for the blast but an Islamic State group affiliate have claimed a string of recent attacks in the province.
Quetta is the capital of Balochistan province, which borders Iran and Afghanistan and has oil and gas resources but is afflicted by Islamist militancy, sectarian violence and a separatist insurgency.
Members of the minority Shiite community and security forces are frequently attacked by militants in the province.