Balochistan National Party (BNP) leader Malik Naveed Dehwar was killed and his guard Haji Essa was injured in the attack, Dawn online reported.
The assailants escaped after spraying bullets at Dehwar’s car, killing him on the spot.
The injured guard was rushed to Quetta Civil Hospital’s trauma centre for treatment.
No group has so far claimed responsibility for the attack.
The BNP has strongly condemned Dehwar’s killing and urged the government to arrest the killers.
Dehwar was a local leader of the BNP, which is led by Sardar Akhtar Mengal, former Chief Minister of Balochistan.
Chief Minister Nawab Sanaullah Zehri also condemned the attack and directed the police to arrest the culprits.
The incident came hours after unidentified assailants attacked the convoy of Balochistan Health Minister Rehmat Saleh Baloch in Panjgur area. The minister and his aides, however, were uninjured in the attack.
Balochistan has been experiencing incidents of violence and targeted killings for over a decade.
The largest province of the country by area, it is home to a low-level insurgency by ethnic Baloch separatists.
Al Qaeda-linked and sectarian militants also operate in the region. The province shares borders with Afghanistan and Iran.