The three were among passengers on a minibus returning to Karachi University after a lunch break on Tuesday when the bomb exploded at the entrance to the university's Confucius Institute, killing the Chinese teachers and a Pakistani national, police and officials say.
A separatist group, the Baloch Liberation Army based in southwestern Balochistan province bordering Afghanistan and Iran, claimed responsibility for the blast, adding in an email to Reuters the attack was carried out by a woman suicide bomber.
It shared in the email a photo of her clad in a long shawl sitting with two children. The photo could not be verified independently by police or other officials.
Karachi police chief Ghulam Nabi Memon said "the reports we have got say they're Chinese". He said they were teachers at the Confucius Institute, a Chinese language and cultural centre.
"The information we've got is that the female bomber was most probably a student at the university," Memon told Geo News TV.
A guard and another Chinese citizen were also wounded in the minibus.
China's foreign ministry strongly condemned the attack and "demanded" Pakistan punish the perpetrators, protect Chinese citizens and prevent such incidents happening again.
"The blood of the Chinese people should not be shed in vain, and those behind this incident will surely pay the price," it said.
The bombing was the first major attack against Chinese nationals in Pakistan since July last year when a suicide bomber blew up a passenger bus in northern Pakistan that killed 13 people, including nine Chinese working on a hydro-power plant.
Other attacks on Chinese working in Pakistan have taken place in Balochistan province, where separatist militants have waged an insurgency against authorities for decades.
Balochistan houses a deep-water port in Gwadar city which Beijing is developing under the China Pakistan Economic-Corridor project as part of President Xi Jinping's Belt and Road initiative to expand trade linkages.
Pakistan's newly elected prime minister, Shehbaz Sharif, condemned what he called a cowardly act of terrorism and promised a speedy investigation.
