The family was traveling in a car when unknown motorcyclists opened fire at them in the posh Hayatabad township here, police said.
Police said the targeted victims belonged to the minority Shia community.
A security guard present at the spot also suffered bullet wounds and later succumbed to his injuries.
Police were investigating the attack.
Earlier this month, Islamic State militants massacred 45 Shia Ismaili Muslims including 17 women in Karachi, in the worst attack targeting members of the minority community.