The "severe attack" occurred in Zabul province's Shinkay district on Saturday, said US military spokesman Lieutenant Colonel Jerry O'Hara.
The two wounded were evacuated to a US base in the southern city of Kandahar for medical treatment, O'Hara said.
"There will be considerable efforts made to find out who is behind these attacks and prevent more like it," he said.
"This incident will not prevent us from accomplishing our mission."
The soldiers' names were not released.
The death brings to 144 the number of US troops killed in and around Afghanistan since Operation Enduring Freedom began in 2001.
After a winter lull, loyalists to the ousted Taliban government and other fighters opposed to the US-backed government of President Hamid Karzai have ramped up their insurgency with a series of bombings and other attacks.