There was no immediate word on the fate of the KC-135 crew. Officials at the U.S. base said they had no information yet on the cause of the crash.
The plane crashed in the afternoon near Chaldovar, a village about 100 miles (160 kilometers) west of the U.S. Transit Center at Manas base, which is outside the Kyrgyz capital of Bishkek. Pieces of the plane, including its tail, lay in a grassy field bordered by mountains; the air was infused with the heavy stench of petrol.
The plane was on a refueling mission for Afghanistan war operations at the time of the crash, a U.S. defense official in Washington said, speaking anonymously because he was not authorized to discuss the details of an ongoing investigation.
Emergency officials said the front section of the plane has not yet been found, the Russian state news agency ITAR-Tass reported from Bishkek.
A resident of the agricultural and sheep-grazing area said the plane exploded in flight.
"I was working with my father in the field, and I heard an explosion. When I looked up at the sky I saw the fire. When it was falling, the plane split into three pieces," Sherikbek Turusbekov told an AP reporter at the site.
The U.S. base, which is adjacent to Manas International Airport outside Bishkek, was established in late 2001 to support the international military campaign in Afghanistan. It functions as an interim point for troops going into or out of Afghanistan and as a home for the tanker planes that refuel warplanes in flight.
The base has been the subject of a contentious dispute between the United States and its host nation.
In 2009, the U.S. reached an agreement with the Kyrgyz government to use it in return for $60 million a year. But the lease runs out in June 2014, and the U.S. wants to keep it longer to aid in the withdrawal of troops from Afghanistan. Kyrgyzstan is reluctant to extend the lease.On Monday, a Boeing 747 cargo plane crashed just after takeoff from the U.S. military base in Bagram, Afghanistan, killing all seven people aboard.
AP writers Jim Heintz in Moscow and Robert Burns in Washington, D.C. contributed to this report.