The van had been heading to an industrial area where the five Japanese nationals worked at Pakistan Suzuki Motors, local police chief Arshad Awan said.
He said police escorting the Japanese returned fire after coming under attack on Friday, killing an accomplice of the suicide bomber whose remains were found from the scene.
"All the Japanese who were the target of the attack are safe," he said.
President Asif Ali Zardari and Prime Minister Shehbaz Sharif denounced the attack on the Japanese nationals.
In separate statements, they praised police for quickly responding and foiling the attack.
They also vowed to eliminate terrorism and prayed for the speedy recovery of those wounded in the attack.
TV news images showed a damaged van as police officers arrived at the scene of the attack.
Awan said the three passers-by who were wounded in the attack were in stable condition at a hospital.
Police were escorting the van after receiving reports about possible attacks on foreigners who were working in Pakistan on various Chinese-funded and other projects, said Tariq Mastoi, a senior police officer.
He said a timely and quick response from the guards and police foiled the attack and both attackers were killed.
No one immediately claimed responsibility but suspicion is likely to fall on a small separatist group or the Pakistani Taliban, which has stepped up attacks on security forces in recent years.
Insurgents have also targeted Chinese who are working in Pakistan on projects relating to the China-Pakistan Economic Corridor, which includes a multitude of mega-projects such as road construction, power plants and agriculture.
In March, five Chinese and their Pakistani driver were killed when a suicide bomber in northwest Pakistan rammed his explosive-laden car into a vehicle when they were heading to the Dasu Dam, the biggest hydropower project in Pakistan, where they worked.
However, Japanese working in Pakistan have not been the target of any such attacks.
Karachi is the largest city in Pakistan and the capital of southern Sindh province.
