Army helicopters and local authorities used loudspeakers on Thursday to urge villagers to leave the area where some of the bloodiest battles have already been fought.
One government official in South Waziristan said Islamabad had been preparing for a decisive action for some time in response to US Secretary of State Colin Powell's recognition of Pakistan's efforts to capture al-Qaida members.
"We have worked out our plans. Targets have been identified. The operation has begun," he said.
But the troops came up against fierce resistance for the third day running, with tribesmen setting fire to a convoy of military vehicles.
Eight army trucks - some loaded with ammunition - along with five other vehicles and two artillery guns were destroyed, residents and an intelligence official told reporters on condition of anonymity.
Sixteen soldiers and 24 rebels were killed in fierce fighting on Tuesday. Eighteen soldiers were reported missing with one official saying he believed they may have been taken captive.
The 40 fatalities marked the beginning of Powell's visit to Pakistan.
The secretary of state announced the US will designate Pakistan a major non-NATO ally, a step that will make it easier for Pakistan's unelected president to buy American military equipment.
Pakistan has for years run into difficulties in obtaining advanced weaponry and aircraft for its military from the United States because of Washington's concerns about its nuclear arms programmes.
Scores of Waziristan locals were
arrested as al-Qaida sympathisers
"We'll designate Pakistan as a major non-NATO ally for purposes of our future military-to-military relations," Powell told a news conference in the Pakistani capital, Islamabad.
Up to 600 suspected al-Qaida members are believed to be hiding in the tribal belt near the Afghan border, where they are protected by Pakistani tribesmen.
Kabul says members of the ousted Taliban government use Pakistan as a base to launch attacks.
The Pakistani operation coincides with a new offensive by 13,500 US-led troops in Afghanistan to track down al-Qaida and Taliban forces on the Afghan side of the frontier.
Various skirmishes have resulted in hundreds of people, including many women and children, being forced to evacuate on tractors and donkeys from Kalosha.
The town has seen some of the heaviest clashes, and is only 15km away from the regional capital of Wana.