Gen David Petraeus, the commander of Nato forces in Afghanistan, is due to hand over command to his successor, Lt Gen John Allen, BBC reported.
Gen Petraeus will start a new role as head of the US CIA in September.
The handover comes hours after a senior aide to Afghan President Hamid Karzai and a lawmaker were killed in an attack in Kabul.
Less than a week earlier, Mr Karzai's half-brother, Ahmed Wali Karzai, was assassinated in Kandahar.
Gen Petraeus, a 37-year veteran of the US Army, is credited with turning around the war in Iraq after former President George W Bush tasked him with managing a surge of troops in 2007.
He took charge last year and oversaw the deployment of more than 30,000 extra US troops to Afghanistan to fight the Taliban.
Gen Petraeus's departure coincides with a security transition as Nato forces begin handing over parts of the country to their Afghan counterparts.