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The aerospace company suggested the technology could provide targets for live-fire training in the future.
Lt. Col. Ryan Inman, Commander, 82nd Aerial Targets Squadron, said: "It was a little different to see an F-16 take off without anyone in it, but it was a great flight all the way around.
"Now we have a mission capable, highly sustainable full scale aerial target to take us into the future."
The plane flew reached 40,000ft (12.2km) and a speed of Mach 1.47 (1,119mph/1,800km/h) and even performed a barrel roll.
Paul Cejas, the project's chief engineer, said: "It flew great, everything worked great, [it] made a beautiful landing - probably one of the best landings I've ever seen."
Boeing said the plane could pull up to 9Gs, something that could adversely affect a human pilot.
The F-16 had previously sat unused for 15 years in Arizona.
Despite the team's enthusiasm, concerns have been raised over the implications of the new technology.
Prof Noel Sharkey of the Campaign to Stop Killer Robots, told the BBC: "I'm very concerned these could be used to target people on the ground.
"I'm particularly worried about the high speed at which they can travel because they might not be able to distinguish their targets very clearly.
"There is every reason to believe that these so-called 'targets' could become a test bed for drone warfare, moving us closer and closer to automated killing"Suggest a correction