The effort is part of SpaceX's push to make spaceflight cheaper by re-using costly rocket and spaceship components after each launch.
SpaceX on Saturday blasted off a shipment of food and supplies for the astronauts on the International Space Station (ISS) using a recycled spaceship.
The last time this particular spaceship flew to space was in 2014.
The refurbished Dragon cargo capsule soared into space aboard a Falcon 9 rocket at 5:07 pm (2107 GMT) from Cape Canaveral, Florida.
"Three, two, one, and liftoff," said NASA spokesman Mike Curie as the rocket blazed a steady upward path into the clouds.
The Dragon is packed with almost 2,700 kilogrammes of science research, crew supplies and hardware and should arrive at the ISS on Monday.
The supplies for special experiments include live mice to study the effects of osteoporosis and fruit flies for research on microgravity's impact on the heart.
The spacecraft is also loaded with solar panels and equipment to study neutron stars.
About 10 minutes after launch, SpaceX successfully returned the first stage of the Falcon 9 rocket back to a controlled landing at Cape Canaveral.
The rocket powered its engines and guided itself down to Landing Zone One, not far from the launch site.
"The first stage is back," Curie said on NASA live webcast, as video images showed the tall, narrow portion of the rocket touch down steadily in a cloud of smoke.
The effort is part of SpaceX's push to make spaceflight cheaper by re-using costly rocket and spaceship components after each launch, rather than ditching them in the ocean.
The launch was the 100th from NASA's historic launch pad 39A, the starting point for the Apollo missions to the Moon in the 1960s and 1970s, as well as a total of 82 shuttle flights.