"Yes I can confirm Shamsi air base is no more under the use of American and 150 US personnel stationed at the base have left," NBC reported quoting senior Pakistani military intelligence officials.
The reports came in hours after US drones struck in North Waziristhan region killing at least 25 people including foreign militants and some women and children.
NBC said the CIA had been using the base close to the Afghan border as a station to launch unmanned predator drones to attack terrorists targets inside Pakistan`s tribal areas.
The TV channel said the base which is also called the Bandari, is a small airfield and air station located about 200 miles southwest of Quetta, along the Afghan border.
The operation of the base -- not publicly acknowledged by the American government -- has always been presumed to have occurred with tacit Pakistani military consent, CNN said.
It was not clear from the Pakistani officials when the presence there began or when it ended.
A US military official who did not want to be identified told CNN: "There are no US forces at Shamsi Air Base in Balochistan." He did not respond at the time or in writing to queries as to whether US personnel had been based there in the past.
The departure of American personnel -- if confirmed -- would be significant because of increasing strain between Islamabad and Washington sparked by the continuing drone attacks and by the Raymond Davis affair, in which a CIA contractor fatally shot two Pakistani men in a Lahore neighbourhood.
CNN quoting American experts said they don`t think the alleged move will affect the effort using drones to target the Haqqani Network and other militant groups holed up in the tribal region.
That`s because many strikes have been conducted from closer bases, such as those across the Pakistani border in eastern Afghan provinces. They said the Pakistanis could be making the alleged move to appease a populace angry at the US.
The southern air base, they said, doesn`t appear to be integral to the tribal area fight and is probably a supporting base.
"It`s not like the Pakistanis shut down the program...
It`s possible they want to do this as a means of pre-empting drone strikes in Balochistan," where there is a Taliban presence.
"The United States has an interest in going after the Taliban in Balochistan" an expert said, and in an ideal world the United States would like to target Taliban sanctuaries in that region with drones.
The reports of closure of base comes after Pakistan`s powerful army chief Ashfaq Parvez Kayani called on US to stop drone strikes on its soil saying the attacks harmed Pakistan`s anti-terror efforts and sparked public anger.
Kayani conveyed this to top US military commander Admiral Mike Mullen during a meeting in Rawalpindi this week.
Mullen had identified the entire North Waziristhan as a hotbed of Haqqani, Taliban and al-Qaeda terrorists planning strikes in neighbouring Afghanistan.
Though Kayani and ISI chief Lt Gen Ahmed Shuja Pasha had raised similar concerns earlier, the US has continued with its deadly drone operations in Pakistan`s restive tribal belt.
It was not immediately clear whether Pakistan`s move to bar the use of its airfield for drone would signal an end of such operations.
The US could use bases in Afghanistan to continue such operations.