One of the attackers died in the shootout near the airport in the city. The rest of the assailants escaped by car, said Syad Kamal Shah, police chief in southern Sindh province.
"Police are looking for who is responsible and what were the motives."
Policeman Hasan Jatoi, who was wounded in the gunfight, said the men shot several of the officers in the head at close range.
Another police officer, Abd Al-Khaliq Shaikh, said the attackers entered the station and shouted "we will not leave any police alive". Shaikh said the attackers fired "dozens of times".
Policeman Muhammad Husayn said the shooting came when he was inside a prayer room at the station, offering morning prayers.
Grabbing his weapon, Husayn returned fire from the prayer room, striking one attacker while taking a bullet in the arm himself.
Authorities had no immediate information on the motive behind the attack and said it would be premature to speculate what group might have been to blame.
"We will not leave any police alive"
Security has been stepped up at police stations around Karachi.
A port city of 14 million, Karachi has seen a series of attacks in recent years.
On 15 March, police defused a huge bomb outside the US Consulate in Karachi, minutes before it was set to explode. Police have not publicised the arrests of any suspects.
Pakistani police defused a bomb
outside US consulate in March
A bomber blew up a truck in front of the consulate in June 2002, killing 14 Pakistanis.
In April 2002, a bomb aimed at the motorcade of Pakistan's President General Pervez Musharraf, a vital ally in the US "war on terrorism", failed to detonate as he travelled through Karachi. Three people were sentenced to 10 years in prison in that attempt.
Tension is also high in Pakistan after a raid involving about 5000 troops on 400 to 500 al-Qaida and other fighters last month in the tribal region of South Waziristan near the Afghan border in which more than 120 people were killed.