The IXV resembles a smaller, robotically controlled version of the US space shuttle, and could provide Europe with a re-useable orbital transportation system of its own
It blasted off on a Vega rocket from South America just after 13:40 GMT.
The test data could also inform future Mars landing technologies.
The demonstrator flew east around the globe, before coming down in the water west of the Galapagos Islands at about 15:20 GMT.
The wedge-shaped IXV (Intermediate eXperimental Vehicle) was designed to gather information on how space objects fall back to Earth.
Commenting on the flight, Esa director-general Jean-Jacques Dordain said: "It couldn't have gone better.
"But the mission itself is not over because now it is necessary to analyse all the data gathered during the flight."
At the time the craft re-entered the atmosphere, it was moving at 7.5km/s. As it pushed against the air, the temperatures on its leading surfaces would have soared to 1,700C.
Flaps and thrusters controlled the trajectory, ensuring the IXV came down close to a recovery ship.
A parachute system deployed in the very late stages of the flight and put the two-tonne vehicle gently in the ocean. Floatation balloons came out to stop it from sinking.
Europe's expertise on re-entry technologies is more limited than, say, the US's or Russia's - something it wants to change with the help of the IXV.
Esa's project manager Giorgio Tumino told BBC News: "Europe is excellent at going to orbit; we have all the launchers, for example. We also have great knowhow in operating complex systems in orbit. But where we are a bit behind is in the knowledge of how to come back from orbit.
"So, if we are to close the circle - go to orbit, stay in orbit, come back from orbit - we need to master this third leg as well as other spacefaring nations."
Esa has already approved a follow-on spacecraft, called Pride, which looks very similar in design to the X-37B, a robotic craft operated by the American military.
No-one is quite sure what missions are flown by the X-37B, but they are likely to include the early testing of new technologies for future satellites.
This could be a role also for Europe's Pride vehicle. In-orbit servicing of satellites is a capability often discussed in this context as well.
Esa nations will meet shortly to define these roles.
"We need still to agree with all the member states all the different types of operations in orbit. But whatever the payload, it will always be in the perimeter space of civilian applications," stresses Mr Tumino.
A prototype for a versatile mini-spaceplane has successfully completed its first test flight, splashing down in the Pacific Ocean.