During the 500-mile journey, the specially adapted plane was controlled by a pilot on the ground, instructed by the National Air Traffic Services.
There were no passengers, but the 16-seater aircraft flew in airspace shared with passenger carriers.
Known as “the Flying Testbed”, it contains on-board sensors and robotics to identify and avoid hazards.
National Air Traffic Services unmanned air vehicle (UAV) expert Andrew Chapman said: “Nats ensured that this test flight was held without any impact on the safety of other users of airspace at the time.
“Although there is still work to be done it would seem that, on the basis of the success of this flight, a UAV could operate in different classes of airspace.”
It is the latest in a series of test flights carried out by Astraea (Autonomous Systems Technology Related Airborne Evaluation and Assessment), which has received £62m funding, from commercial companies and the UK government, to research how civilian unmanned aircraft could fit in to shared airspace.
A representative of BAE Systems, one of the companies to have invested in Astraea, said: “The flights were part of a series of tests helping flight regulators and Nats to understand how these flights work, and what they need to do were they to go ahead and put a regulatory framework in place for the unmanned flights in manned airspace.
“It’s still very early days in terms of that regulation taking place.”
Business and Energy Minister Michael Fallon described the latest flight as “pioneering”.
Astraea has made significant achievements, placing the UK industry in a good position globally on unmanned aircraft and the development of regulations for their civil use,” he said.
The project has the support of the Civil Aviation Authority (CAA).
At a media conference last year, Astraea project director Lambert Dopping-Hepenstal said getting unmanned aircraft (UA) into shared airspace was more than a technical challenge.
“It’s not just the technology, we’re trying to think about the social impact of this and the ethical and legal things associated with it,” he said.
“You’ve got to solve all this lot if you’re going to make it happen, enable it to happen affordably.”