The privately owned cargo ship splashed down in the Pacific right on target, 250 miles off the coast of Mexico's Baja Peninsula, five hours after leaving the orbiting lab. The California-based SpaceX confirmed the Dragon's safe arrival via Twitter.
"Special delivery! Dragon now being recovered in the Pacific," the company said in a tweet.
The capsule brought back more than 1 ton of science experiments and old station equipment, as well as 13 toy sets of Lego building blocks that were used by space station crews over the past couple years to teach children about science.
It's the only supply ship capable of two-way delivery. With the space shuttles retired, NASA is paying SpaceX more than $1 billion for a dozen resupply missions.
The unmanned capsule will be shipped to Los Angeles - arriving Wednesday night - and then trucked to Texas for unloading.
Earlier in the day, astronauts released the unmanned capsule from the end of the space station's giant robot arm. The 250-mile-high parting was a poignant moment for the three space station's residents, who helped to snare the Dragon three weeks earlier.
"Sad to see the Dragon go," astronaut Thomas Marshburn told Mission Control. "Performed her job beautifully. Heading back to her lair. Wish her all the best for the splashdown today."
The Dragon used old-NASA-style parachutes to plop into the ocean; company officials indicated all appeared to go well during the re-entry.
SpaceX launched the capsule from Cape Canaveral at the beginning of March. Mechanical trouble delayed the capsule's arrival at the space station by a day. SpaceX flight controllers at company headquarters in Hawthorne, Calif., managed to fix the problem within hours.
Bad weather at mission's end in the Pacific recovery zone kept it in orbit an extra day.
Once the Dragon pulls into port, NASA will retrieve the science samples meticulously collected over the weeks and months by space station astronauts, as well as experiments that flew up with Dragon, including hundreds of flowering weeds. Mouse stem cells stayed behind on the space station, at the request of the Japanese researchers.
Old space station equipment and other items aboard the Dragon will be removed by SpaceX in McGregor, Texas. In all, more than 1 ton of gear - 2,668 pounds - was loaded into the capsule.
SpaceX - Space Exploration Technologies Corp. - is run by billionaire Elon Musk, who made his fortune as a co-creator of PayPal. He also owns the electric car maker Tesla Motors.
This was the second flight of a Dragon to the space station under the $1.6 billion contract with NASA, and the third delivery mission altogether for SpaceX. The next flight is slated for late fall.
A competitor, Orbital Sciences Corp. of Dulles, Va., plans a test flight of its Antares rocket and a dummy payload next month. That launch will be conducted from Wallops Island, Va. Orbital, too, has a NASA contract to deliver supplies.
Russia, Japan and Europe also periodically send up supplies, but SpaceX has the only craft capable of returning goods. All the others burn up upon re-entry.
Three astronauts are aboard the space station right now. They will be joined by three more following Thursday's Soyuz launch from Kazakhstan.
With its space shuttles now museum pieces, NASA is paying Russia to launch U.S. astronauts until SpaceX or another American company comes up with spaceships than can safely fly crews. Musk anticipates that happening by 2015 with a modified Dragon.