The victims were returning home after offering Friday prayers at the Najaf Imambargah in north Karachi, they said.
"They had just left the Imambargah on their motorcycles when they were attacked," police officer Arab Mahar said.
Police suspect the incident to be a sectarian attack.
Karachi in the past has been rocked by sectarian violence but today's murders were the first sectarian killing in the city this year.
Due to the ongoing security crackdown on criminals in the city, incidents of target killings and sectarian violence have decreased but Shia Muslims have continued to be victims of attacks.
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