Security round the airport was tightened and an investigation into the "terrible, senseless crime" was under way, said Boris Rhein, interior minister for Hesse state.
"Whether the incident was linked to terrorism I cannot say at this stage," he told reporters.
The suspected gunman was apparently a Kosovo national, he said. Police said he was 21.
A spokesman for Frankfurt airport operator Fraport said the shooting took place in a U.S. Army bus in front of Terminal 2. U.S. President Barack Obama said he was outraged by the attack.
Authorities in Kosovo believed they knew the identity of the suspected gunman but could not confirm it yet, Kosovo Interior Minister Bajram Rexhepi told Reuters in Pristina.
A police official identified the man as Arif Uka from the city of Mitrovica but no official confirmation was given yet.
"The government of the Republic of Kosovo is extremely touched and strongly condemns the killing of two American citizens and the wounding of two others by a citizen from Kosovo that happened today in Germany," the government said in a statement.
The United States has had troops in Kosovo since 1999, when a NATO bombing campaign pushed out Serbian forces. The U.S. troops there now are helping to oversee a fragile peace that has held since Kosovo declared independence from Serbia in 2008.
Major Beverly Mock, spokeswoman for the U.S. Air Force at Rammstein air base in Germany, said the identities of the dead airmen had not yet been confirmed.
"The German authorities have the shooter in custody," she said.
Chancellor Angela Merkel, speaking in Berlin, told a news conference: "We don't know the details but I would like to express how upset I am. We have to do everything we can to find out what happened."
