Malik Naveed Dehwar, a leader of Balochistan National Party (BNP), and his guard were shot dead in Quetta city, police said.
Some unidentified gunmen opened fire at Dehwar's vehicle and fled from the spot.
Police said Dehwar died at the spot while his guard succumed to his injuries later in the 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.
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The party is headed by Sardar Akhtar Mangal, a former chief minister of Balochistan.
Earlier in the day, the health minister of Pakistan's restive Balochistan province survived a rocket attack when unidentified assailants targeted his convoy.
The law enforcement personnel have cordoned off the area for investigation.