Earlier Sunday, 21 tribal policemen believed to have been kidnapped by the Taliban were found shot dead in Pakistan's troubled northwest tribal region, government officials said.
Reports conflicted about whether the car bombing was a suicide attack or the device was detonated remotely.
Pakistan has experienced a spike in killings over the last year by radical Sunni Muslims targeting Shiites, whom they consider heretics. The violence has been especially pronounced in Baluchistan province, where the latest attack occurred.
In addition to the 19 people killed in the bombing in Baluchistan's Mastung district, 25 others were wounded, many of them critically, said Tufail Ahmed, a local political official. The blast destroyed the bus and damaged a nearby bus also carrying Shiites.
Ahmed and a person who was riding in the second bus, Mohammed Ayan Danish, said the attack was carried out by a suicide bomber.
The bomber "rammed a small car into the first bus, which contained 43 pilgrims," said Danish.
But Akbar Durrani, the home secretary in Baluchistan, said the explosion was caused by a car packed with explosives that was parked beside the road and detonated by remote control.
The pilgrims who were targeted were headed to Iran, a majority Shiite country that is a popular religious tourism destination, Ahmed said.
Shiites make up around 15 percent of Pakistan's 190 million people. Baluchistan has the largest community, mainly made up of ethnic Hazaras, identifiable from their facial resemblance to Central Asians.
An escalation in recent years of Sunni extremists' attacks against Shiites in Pakistan has been fueled mainly by the group Laskar-e-Jangvhi, aligned to Pakistani Taliban militants in the tribal region. More than 300 Shiites have been killed in Pakistan this year, according to Human Rights Watch.
The violence has pushed Baluchistan deeper into chaos. The province was already facing an armed insurgency by ethnic Baluch separatists who frequently attack security forces and government facilities. Now the secessionist violence has been overtaken by increasingly bold attacks against Shiites.
The sectarian bloodshed adds another layer to the turmoil in Pakistan, where the government is fighting an insurgency by the Pakistani Taliban and where many fear Sunni hard-liners are gaining strength. Shiites and rights group say the government does little to protect Shiites and that militants are emboldened by their perceived links to Pakistan's intelligence agencies.
The 21 tribal policemen who were shot dead were found shortly after midnight Sunday in the Jabai area of Frontier Region Peshawar after being notified by one policeman who escaped, said Naveed Akbar Khan, a top political official in the area. Another policeman was found seriously wounded, Khan said.
The 23 policemen went missing before dawn Thursday when militants armed with rocket-propelled grenades and automatic weapons attacked two posts in Frontier Region Peshawar. Two policemen were killed in the attacks.
Militants lined the policemen up on a cricket pitch late Saturday night and gunned them down, said another local official who spoke on condition of anonymity because he was not authorized to talk to reporters.
Also Sunday, two Pakistani army soldiers were killed by a roadside bomb in the North Waziristan tribal area, the main sanctuary for Taliban and al-Qaida militants in the country, security officials said, speaking on condition of anonymity in line with official policy.
U.N. Secretary-General Ban Ki-moon condemned the escalating violence, especially the continuing targeting of religions minorities, U.N. spokesman Martin Nesirky said.
"These cruel acts of violence cannot be justified by any cause or grievance," Ban's spokesman said. "Their perpetrators should be brought to justice."
The secretary-general stressed the U.N.'s solidarity and support for the government and people of Pakistan and "their efforts to defend their country's institutions and freedoms in the face of the scourge of terrorism," Nesirky said.
Associated Press writers Riaz Khan and Rasool Dawar in Peshawar, Pakistan, contributed to this report.