The blast is believed to be the first attack on U.S. embassy officials in Kabul in months.
The blast that killed U.S. troops occurred in Zabul province's Daychopan district, the military said in a statement. The three wounded soldiers were hit by shrapnel and were in stable condition, the military said.
"The unit was conducting offensive operations in support of an ongoing mission to find and defeat enemy forces in the area when the attack occurred," the statement said.
"The unit's mission is part of a much larger operation to disrupt enemy forces and to thereby provide a safe environment for upcoming September elections."
The statement quoted Maj. Gen. Jason Kamiya, the U.S.-led coalition's operational commander, as saying the attack would "strengthen, not weaken, the resolve" of the force.
Some 187 U.S. service members have been killed in and around Afghanistan since the start of Operation Enduring Freedom in late 2001 - including 64 during an upsurge of insurgent attacks in the last six months that also have left about 1,000 others dead.
On Friday, a U.S. Marine was killed in a clash near Asadabad in eastern Afghanistan, while a day earlier, a roadside bomb killed two U.S. soldiers protecting road workers on a U.S.-funded project in southern Kandahar province, a former Taliban stronghold.
U.S. officials have warned that fighting could escalate ahead of the parliamentary and provincial assembly elections, seen as the next step in building Afghanistan's democracy after a quarter-century of civil strife and war.
In attacks elsewhere, a roadside bomb exploded late Saturday under a police vehicle also in Zabul province, killing two police officers, said local government chief Rozi Khan.