Early on Thursday, Mir Zafarullah Jamali left Karachi, the provincial capital, for Badin, the worst-affected among Sindh's flood-hit districts.
More than 100 people have died in floods in the province in recent days.
Rescue and relief efforts have been stepped up, and troops are helping deal with the emergency.
Officials say more than 400,000 people have been stranded across Sindh after a week of heavy downpour.
Thousands of people made homeless by torrential rains and resulting floods have sought shelter in temporary relief camps.
Urgent measures
Prime Minister Jamali is scheduled to supervise rescue and relief efforts in Badin, where most flood victims live, and then fly to other affected areas.
Local administrations have established temporary relief camps in schools, colleges and government offices across the province.
These have filled up rapidly, with some reports suggesting over 65,000 homeless people have sought shelter.
But demand is stretching supplies. Officials say they have not been able to feed all the people registered at the camps.
"Even now, there are thousands of people we have been unable to reach," Badin district police chief Javaid Akhtar Odoh told the Reuters news agency.
Officials say some 5,000 villages in five districts have been badly hit, and the situation in Karachi, Pakistan's commercial capital, is equally grim.
On Wednesday, Mr Jamali flew over severly affected parts of Karachi, and ordered urgent relief and reconstruction measures.
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