Three attackers were also killed in the assault on the consulate in the city's high-security red zone, according to a Pakistan foreign ministry spokesman.
The Baloch Liberation Army, a separatist group, claimed responsibility for the attack in a tweet including a photo of three unidentified men and the message: "Karachi: Fidayeen of BLA attacked the Chinese embassy in Karachi."
"Fidayeen" is an Arabic term that loosely translates as "one who sacrifices himself."
In a statement released after the attack, the group said its objectives were "clear -- we will not tolerate any Chinese military expansionist endeavors on Baloch soil."
CNN does not have independent confirmation of the group's involvement.
Security was immediately ramped up at consulates all over Karachi, Sindh Governor Imran Ismael told CNN.
Two of the four victims were uniformed police officers, according to Seemi Jamali, the Head of Emergency at Jinnah Hospital. No Chinese nationals were among the dead, the hospital said.
Pakistan's Prime Minister Imran Khan condemned the attack, ordering a "complete inquiry."
In a statement, Khan called it "part of conspiracy against Pakistan and China's economic and strategic cooperation. However, such incidents will never be able to undermine the Pakistan-China relationship that is mightier than Himalaya and deeper than Arabian sea."