The soldiers were fired on by militants south of Tirin Kot, about 250 miles southwest of the capital, Kabul, in Uruzgan province, said military spokesman Lt. Col. Tucker Mansager.
Spokeswoman Capt. Cindy Beam said the soldiers were attacked during a patrol through Uruzgan and Kandahar provinces.
She gave no further details of the clash, but said the injured Marine underwent surgery at the U.S. military base near Kandahar city for "multiple gunshot wounds to the lower extremities."
She did not give further details about the soldier's condition, and neither victim was identified.
A 2,000-strong Marine force was recently deployed in Uruzgan to bolster the fight against resurgent Taliban-led militants. It was unclear if the two were part of that force. Marines are also operating in eastern Kunar province and guard facilities including the U.S. Embassy in Kabul.
The troops from the special operations-capable 22nd Marine Expeditionary Unit, based in Camp Lejeune, North Carolina, began arriving in Afghanistan in late March and have set up a new base near Tirin Kot, the Uruzgan provincial capital.
Mansager said the U.S.-led coalition in Afghanistan had swelled to 20,000 — up from about 11,000 late last year.
Part of the increase was down to "overlap" during a routine rotation of units, he said, but declined to say how many would remain once the switch is complete.
Despite the extra forces, Taliban-led militants have carried out a fresh wave of attacks, killing dozens of Afghan troops. A Taliban spokesman claimed its fighters on Wednesday killed two British security consultants helping the United Nations organize elections due in September.
Mansager declined to discuss the Marines' operations, but said forces would likely "bump into more terrorists" in southern and eastern Afghanistan.
Uruzgan, the home province of Taliban supreme leader Mullah Omar, is widely considered a stronghold of the ousted hardline militia. Some observers believe the one-eyed fugitive leader could be in the region.
Some 121 U.S. soldiers have died, 53 of them in combat, since Operation Enduring Freedom began in Afghanistan in late 2001, toppling the Taliban regime for harboring al Qaeda.
Still, one-third of those casualties have occurred in other countries where the U.S. military has mounted counterterrorism operations.
Previously, the only Marines killed in Afghanistan were two who died when. Seven more died plane carrying fuel crashed in neighboring Pakistan the same month.
Four U.S. soldiers have been killed in action since Operation Mountain Storm, the military's latest effort to crush Taliban and al Qaeda resistance in Afghanistan, began in early March.
By Stephen Graham