Malik Naveed Dehwar, a leader of Balochistan National Party (BNP), was in his vehicle when gunmen opened fire at him in Quetta city and fled from the spot, police said.
Police said Dehwar died at the spot while his guard succumed to his injuries later in a hospital. Another person was also injured in the firing and was admitted to a hospital.
"No group has claimed responsibility for the target killings as yet," a police official said.
The BNP central leadership condemned the attack and said it highlighted the law and order situation in the province.
The incident came hours after unidentified assailants attacked the convoy of Balochistan Health Minister Rehmat Saleh Baloch in Panjgur area, with the minister and his aides remaining unharmed in the incident.
The law enforcement personnel have cordoned off the area for investigation.
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.
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