The scheme for a pilotless aircraft built by the three EU powers could be worth up to a billion euros ($1.2 billion) if it gets airborne, officials said after the deal was signed in Brussels.
"The goal of the Euro-drone is that we can decide by ourselves in Europe on what we use it, where we deploy the Euro-drone and how we use it," German Defence Minister Ursula von der Leyen said.
"This makes us, the Europeans, independent."
For a decade, European powers have tried and failed to come up with a common drone project, meaning that Britain, Italy and France currently use US-made Reaper drones. Germany and France also use Israeli-built machines.
The three countries first agreed to cooperate on an unmanned aerial vehicle (UAV) in 2013.
The medium-altitude, long-endurance European drone will be designed for intelligence and reconnaissance missions and will be able to carry a "variety of payloads," according to a statement after the signing.
Airbus, France's Dassault Aviation and Italy's Alenia Aermacchi are behind the proposal.
French Defence Minister Jean-Yves Le Drian said the Euro-drone deal was a "very important step for European cooperation."
Other European countries including Spain and Poland could get involved at a later stage, officials said.
The two-year technical assessment will try to find common ground between Germany, France and Italy on operational needs, performance, timing and cost, they said.