The assailants then gunned down 14 of the passengers while two other people removed from the bus managed to escape to a nearby checkpoint.
Almost 20 armed assailants wearing Frontier Corps uniforms stopped the bus and handpicked their victims in the dead of night, Pakistan's Dawn newspaper reported, citing senior Balochistan police officers.
Going towards Gwadar through Makran Coastal Highway Ormara comes in midway between Karachi and Gwadar, the Arabian Sea port town where China is building a deep-water port.
Balochistan Inspector General of Police Mohsin Hassan Butt said around 15 to 20 unidentified gunmen wearing uniforms of paramilitary Frontier Corps were involved in the attack carried out early morning at Buzi Top area.
Gunmen reportedly stopped a few buses, checked the identity cards of passengers, and offloaded about 16 people.
Provincial home minister Mir Zia Langov told AFP a full-scale investigation had been launched into the attack, and authorities are trying to track down the gunmen, who he said had fled the scene.
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No group has claimed responsibility for the attack.
Balochistan Chief Minister Jam Kamal condemned the incident and offered his condolences to the victims' families.
He termed the attack as "an act to build a conspiracy to halt progress in Balochistan and tarnish the state's image".
President Dr Arif Alvi also condemned the "cowardly terrorist attack".
The Balochistan area has seen an increase in terrorist attacks in the past few weeks, most recently on April 12 when an improvised explosive device exploded in a vegetable market, killing 20 people. He said "the nation was united and steadfast in its fight against terrorism". He said that coordinated terrorist attacks in the country are hinting at the involvement of the enemies of Pakistan.
PPP Chairman Bilawal Bhutto-Zardari also condemned the killings.