The attack took place in southern Afghanistan on Saturday, a statement from the Nato-led Resolute Support mission said.
It was not immediately clear who carried out the attack, or whether they had been apprehended.
However, the statement said it was “an apparent insider attack”.
The two wounded service members are in a “stable” condition, Nato said, adding it would not be releasing any further details until next-of-kin had been informed.
But a police officer told news agency AFP the shooting happened at the airport in Tarinkot, the capital of Uruzgan province – although they were unable to confirm this detail with any Nato officials.
The Taliban have also released a statement, saying an Afghan soldier opened fire on US soldiers in Uruzgan.
The attack comes a year after three US special forces soldiers were shot deadby one of their Afghan colleagues. It was claimed by the Taliban.
However, these kind of attacks – where local troops turn on international forces and often referred to as “green on blue” incidents – are not necessarily the work of militants infiltrating the security forces.
Cultural misunderstandings and combat stress have also been named as the cause in previous attacks.
The US still has an estimated 14,000 troops in the country helping support the Afghan military, despite Nato’s combat mission in Afghanistan officially ended in 2014.