The International Security Assistance Force (ISAF) announced the takeover in a statement hours before an official ceremony was due in the southern city of Kandahar to mark the transfer of authority.
The ISAF force, which has been under NATO command since 2003, has already been operating in western and northern Afghanistan and the capital Kabul.
Its expansion south gives it six more provinces: Day Kundi, Helmand,
Kandahar, Nimroz, Uruzgan and Zabul.
Most of them see some of the worst of the Taliban insurgency, which sees regular suicide and roadside bombings.
"ISAF will bring in the presence of more international military forces and will continue the efforts of the coalition to provide security as well as reconstruction projects and humanitarian assistance," the statement said.
The transfer of authority "demonstrates to the Afghan people that there is
a strong commitment of the part of the international community to further extend security into the southern province," said coalition commander
Lieutenant General Karl Eikenberry.
"NATO is here for the long-term, for as long as the government and people of Afghanistan require our assistance," the ISAF commander, British Lieutenant General David Richards, said in the statement.
"We are committed to Afghanistan and its future."