The attack happened in Kurram, a district in northwestern Khyber Pakhtunkhwa province where sectarian clashes between majority Sunni Muslims and minority Shi'Ites have left dozens of people dead in recent months.
No one has claimed responsibility.
The latest violence came a week after authorities reopened a key highway in the region after keeping it closed for weeks following deadly clashes.
Local police official Azmat Ali said several vehicles carrying passengers were travelling in a convoy from the city of Parachinar to Peshawar, the capital of Khyber Pakhtunkhwa, when gunmen opened fire.
He said at least 10 passengers were in a critical condition at a hospital.
Pakistani President Asif Ali Zardari condemned the attack and offered his condolences to the families of the victims.
He ordered authorities to take action against those who orchestrated the attack.
Baqir Haideri, a local Shi'Ite leader, denounced the assault, saying "the terrorists martyred our innocent people after identifying them".
He said the death toll from the attack is likely to rise.
Shi'Ite Muslims make up about 15 per cent of the 240 million population of Sunni-majority Pakistan, which has a history of sectarian animosity between the two communities.
Although they live together largely peacefully in the country, tensions have existed for decades in some areas especially in parts of Kurram - where Shi'Ites dominate.
Nearly 50 people from the two sides were also killed over a land dispute in July when clashes between Sunni and Shi'Ites erupted in Kurram.
Pakistan is currently carrying out intelligence-based operations to tackle violence in the northwest and southwest, where militants and separatists often target police, troops and civilians.
Most violence in these areas has been blamed on the Pakistani Taliban and the outlawed Baloch Liberation Army.
