The ship was released by the space station's giant robotic arm, controlled by astronaut and station commander Steven Swanson. Let go, the craft fell from orbit 260 miles above the South Pacific -- gravity returning it to the sea. The latter portion of its descent was slowed by parachutes.
Launched to deliver supplies, Dragon returned home hands full, its cargo load packed with 3,500 pounds of completed science experiments and equipment.
"Very nice to have a vehicle that can take your science, equipment and maybe someday even humans back to Earth," Swanson told Mission Control.
Currently, Dragon is the only supply ship able to safely return material to Earth. Other supply capsules burn up in the atmosphere upon re-entry.
Splashing down some 300 miles off the coast of Baja California, Dragon will be towed back to port outside Los Angeles.
Dragon's cargo features a freezer packed with scientific samples, the results of several different space station experiments, including an attempt to understand why antibiotics are less effective in microgravity.
"The space station is our springboard to deep space and the science samples returned to Earth are critical to improving our knowledge of how space affects humans who live and work there for long durations," said NASA scientist William Gerstenmaier.
"Now that Dragon has returned, scientists can complete their analyses," Gerstenmaier added, "so we can see how results may impact future human space exploration or provide direct benefits to people on Earth."