US General David Petraeus has taken control of US military operations throughout the Middle East and much of Asia as head of US Central Command.
His responsibilities include Iraq, Afghanistan, Pakistan and Iran.
At a change-of-command ceremony at Central Command headquarters, US Defence Secretary Robert Gates said he was "precisely the man we need".
Previously Gen Petraeus was commander of the US military in Iraq, and widely credited with improving security.
Iraq and Afghanistan are likely to dominate Gen Petraeus' agenda, says the BBC's defence correspondent Rob Watson.
In Iraq, Gen Petraeus will have to manage the eventual reduction of US forces, a process he has made clear that he does not favour rushing.
During his time there, Gen Petraeus implemented the "surge" plan, which saw nearly 30,000 US troops deployed to troublespots in Iraq.
In a major change of strategy, coalition forces also moved out of large bases and into highly populated areas.
Since then, the security situation has improved markedly, with less violence and fewer deaths, and progress on both the political and economic fronts.
But he has said that security gains were "not irreversible" and that the US still faced a "long struggle".
On Afghanistan, he has already commissioned a major review of US strategy, which is expected to emphasise the need for a wider regional solution and more outreach to the Taleban.
The US Assistant Secretary of State for South and Central Asian Affairs, Richard Boucher, told the BBC's World Today that it was unlikely there would be talks between Gen Petraeus and the Taleban.
"We're not talking about the US talking to the Taleban. The issue is that both Afghanistan and Pakistan have policies on reconciliation and we have been, and continue to be, willing to support those policies."
He added: "Everybody's got a rumour about some commander who might be willing to lay down his arms and stop fighting.
"But none of that has ever materialised, because those guys just keep hijacking buses and chopping heads off."
The extent of Gen Petraeus' future influence on US policy in the region will of course depend to some extent on who wins the presidential election, though both candidates are admirers, our correspondent says.
Whatever happens, the ambitious and reflective general, whose academic achievements rival his battlefield experience, is likely to remain a prominent and powerful figure, our correspondent adds.