The incident took place on Sharae Faisal near Natha Khan area when the gunmen opened fire on his vehicle around 5:30pm.
The journalist was on his way to his office from the airport when he was attacked.
“Four gunmen riding on motorbikes started firing at the car near Karsaz (around six kilometres from Jinnah International Airport) when Mir's car was passing through, he received three bullets in the lower parts of his body,” said senior police official Peer Muhammad Shah.
Shah said a single gunman first opened fire on Mir's car, followed by others who chased him on motorcycles.
Karachi police chief Shahid Hayat said Mir suffered three gunshot wounds to the stomach and the upper legs.
“Hamid Mir has received three bullets but the doctors told me that he is out of danger,” Karachi police chief Shahid Hayat told news agency AFP.
Mir's colleague Rana Jawad said he had talked briefly to Mir on his mobile phone as he was under attack.
“I spoke to him briefly when he was escaping, he said they have shot him and now they were following him,” said Jawad.
“He has been shot thrice, in the pelvic, abdomen and thighs,” he added.
Mir was taken to a private hospital for emergency treatment. The journalist was taken to the hospital in a state of unconsciousness.
Following a surgery lasting two-and-a-half hours, hospital administration said the journalist's condition was stable, but that he would be kept under observation.
Friends and colleagues said Mir had previously told them that if he is attacked, Pakistan's intelligence agency, the Inter-Services Intelligence (ISI), “and its chief Lt General Zaheerul Islam will be responsible”.
Speaking to Geo News, his brother Amir Mir said the senior anchorperson had visited him and informed him of what he called a plan hatched by Lt-Gen Islam to assassinate him.
Geo News, the media organisation for which Mir works, reported that he had also sent a recorded video to Committee to Protect Journalists (CPJ) implicating the ISI in any attempt on his life.
Meanwhile, a spokesman for the ISPR, the military’s public relations wing, condemned the attack on Hamid Mir, and said an independent inquiry must be carried out to ascertain facts behind the attack.
“However raising allegations against the ISI or the head of ISI without any basis is highly regrettable and misleading,” he said.
Shortly after the attack, messages of condemnation started pouring in against the attack the seasoned journalist's life.
In a message, President Mamnoon Hussain condemned the attack and expressed sorrow at the incident.
Social media also exploded with messages of condemnation.
No militant group has so far accepted responsibility for the attack.
This is not the first time an attempt has been made on Mir's life.
In November 2012, Mir narrowly escaped a bid on his life when the bomb disposal squad defused a bomb planted under his car in Islamabad. The Tehreek-i-Taliban Pakistan (TTP) had accepted responsibility for the attempt and said it was targeting the journalist due to his "secular agenda".
Last month, a gun attack attack on noted columnist and TV anchor Raza Rumi in Lahore led to the death of his driver.
Rights groups say Pakistan remains one of the most dangerous countries in the world for working journalists.
According to media watchdog group Reporters Without Borders, seven reporters lost their lives in the line of duty in 2013 in the country.
Earlier in March, Pakistan announced it would set up a special commission to protect journalists and will include press freedom as part of peace talks with the Taliban.
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