Some 200,000 people have been evacuated in the Thatta area of Sindh province, where dozens of villages are submerged.
In the north, workers have begun clearing up as the floods recede. The UN has appealed for more helicopters to reach 800,000 people who are cut off.
Doctors in many areas are struggling to cope with the spread of water-borne diseases such as diarrhoea and cholera.
Five million Pakistanis have no shelter, and urgently need tents or plastic sheeting to protect them from the sun.
The UN says more than 17 million people have been affected by the monsoon floods, and about 1.2 million homes have been destroyed.
Health alert
The vast body of flood-water that has swept the length of Pakistan is now threatening previously unaffected communities in Sindh province, at the country's southern tip.
The authorities have been organising a mass evacuation from the town of Thatta - near the mouth of the Indus delta - and surrounding villages.
At the moment, all that stands between locals and the vast weight of water is an embankment which has started to crack in places. If it bursts, the whole area could be submerged.
"We are very vigilant, we are watching and we are strengthening wherever we see any weakness on these protection walls," Manzoor Ali Sheikh, a senior local official in Thatta told the BBC.
"We are hopeful that they will not give way to the water and water will pass through these bunds (embankments) to the sea."
The Indus river at Hyderabad, just north of Thatta, is already at a 50-year high and there are fears the level could rise even further.
Elsewhere in Sindh people are still battling to hold back the flood-waters.
The town of Qubo Saeed Khan, near Shahdadkot in the north of the province, has been completely inundated, reports the BBC's Chris Morris from the area. He says tens of thousands of people have already been evacuated from the town.
The task of coping with disease and urgent humanitarian needs across Pakistan is being made more difficult by the sheer number of people cut off by the floods.
An estimated 800,000 people are still stranded, the UN says - many in the mountainous north-west, where roads and bridges have been swept away.
The US has deployed at least 18 helicopters to fly regular relief missions, but the UN said it would need at least 40 more heavy-duty aircraft working at full capacity to reach those who have been cut off.
Shattered infrastructure
On Tuesday, Pakistan's Prime Minister Yousuf Raza Gilani told a meeting of senior doctors, health ministry officials, UN representatives and members of non-governmental organisations that Pakistan was experiencing "the worst natural calamity of its history".
UN officials are quoted saying that 1.6 million people are already affected by water-borne diseases such as cholera, diarrhoea and dysentery.
"In the past one day alone, more than 100,000 people were sick and required different kinds of treatment," a World Health Organization spokesman, Paul Garwood, told the BBC.
"I understand most of them were for skin infections, for diarrhoea, for acute respiratory infections and, as well, malaria."
The World Food Programme says it already has enough food in Pakistan to feed six million people for a month but distribution has been hampered by a lack of resources and the country's shattered infrastructure.
Pakistani officials have been meeting the IMF in Washington this week to discuss easing restrictions on an $11bn (£7bn) loan package.
Officials say the floods have destroyed more than 17,000 sq km (6,600 sq miles) of land, which will have a significant impact on the agricultural sector and the country's economic growth.
