The troops were patrolling with Afghan forces when their vehicle struck a bomb Tuesday afternoon, the U.S. military said in a statement. The military did not release the location of the attack pending the notification of relatives.
The previous deadliest attack against U.S. forces this year was an explosion in Zabul province in January that killed three troops.
Twenty-nine Americans troops have died in Afghanistan this year, far surpassing the eight U.S. forces killed in the first two months of 2008.
The U.S. is increasing troop levels in Afghanistan. A record 38,000 U.S. forces now operate in the country, many in Taliban strongholds in the dangerous south.
President Barack Obama last week announced the deployment of 17,000 more troops to Afghanistan, adding to the 38,000 American forces already fighting a strengthening insurgency. Taliban militants have increased attacks the last three years and now hold sway in large areas of countryside.
Taliban bombs once caused relatively few casualties among soldiers in armored vehicles, but more powerful charges now cause massive damage even to well protected Humvees.
In a separate incident in southern Helmand province on Monday, coalition and Afghan forces killed 16 militants when responding to gunfire from insurgents on their convoy, the U.S. said in another statement. There were no other reports of casualties, the statement said.