A recycled Dragon spacecraft and Falcon 9 rocket blasted off at 10:36 am (local time).
Meanwhile, the Dragon headed for the International Space Station (ISS). And the rocket did just that, releasing the supply capsule into the planned preliminary orbit 10 minutes after liftoff.
The crewmembers on ISS will use a 57.7-foot robotic arm to reach out and capture the Dragon spacecraft and attach it to the station on December 17. From there, the cargo ship will be pulled in for berthing at the Earth-facing port of the station's forward Harmony module.
The first time NASA experimented with re-using a spacecraft was long before the Space Shuttle, way back in 1966.
For the past two years, the private SpaceX has been salvaging as much as possible from rockets following liftoff.
SpaceX has now managed to return 20 of its rocket boosters after launch, whether on land or on a floating ocean platform, as part of its effort to re-use instead of jettison costly components.
Space X made a historic attempt by successfully lifting up a recycled rocket and a spaceship into space.
This was the first launch from the SpaceX-rented Complex 40 in more than a year. The rocket was a SpaceX Falcon 9, and the cargo vehicle was a SpaceX Dragon capsule. SpaceX spent $50 million rebuilding the pad.
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Jessica Jensen, a SpaceX manager, said the company aims to reuse rockets - and capsules - far more than twice.
As live images showed the first stage glide down, steady and upright, from the air to the launchpad, cheers erupted at SpaceX's Hawthorne, California headquarters, where employees regularly gather to watch rocket launches.
Three minutes later, the booster and second stage of the rocket separated.
Finally, dropping like a stone toward Landing Zone 1 at the Air Force station, a single engine restarted, four landing legs extended and the booster settled to a smooth touchdown on a circular pad known as Landing Zone 1.
This time, the capsule is hauling nearly 2270kg of goods, including 40 mice for a muscle-wasting study, a first-of-its-kind impact sensor for measuring space debris as minuscule as a grain of sand and barley seeds for a germination experiment by Budweiser, already angling to serve the first beer on Mars.
Mounted in an unpressurized "trunk" section are two external science packages, one to measure how much solar radiation Earth receives and another to help characterize the space debris environment.
The mission is SpaceX's 13th of 20 under a $1.6 billion contract with NASA.
Soyuz MS-07 commander Anton Shkaplerov, NASA flight engineer Scott Tingle and Japanese astronaut Norishige Kanai are scheduled to dock at the station's Rassvet module early Tuesday.