SpaceX CRS-21, also known as SpX-21, was a Commercial Resupply Service mission to the International Space Station which launched on 6 December 2020. The mission was contracted by NASA and was flown by SpaceX using a Cargo Dragon 2. This was the first flight for SpaceX under NASA's CRS Phase 2 contract awarded in January 2016. This was also the first Cargo Dragon of the new Dragon 2 variant, as well as the first Cargo Dragon flight that was docked at the same time as a Crew Dragon spacecraft. This mission used Booster B1058.4, becoming the first NASA mission to reuse a booster previously used on a non-NASA mission. This was also first time SpaceX launched a NASA payload on a booster with more than one previous flight.

Commercial Resupply Services (CRS) are a series of flights awarded by NASA for the delivery of cargo and supplies to the International Space Station (ISS) on commercially operated spacecraft. The first CRS contracts were signed in 2008 and awarded $1.6 billion to SpaceX for twelve cargo Dragon and $1.9 billion to Orbital Sciences for eight Cygnus flights, covering deliveries to 2016. The Falcon 9 and Antares rockets were also developed under the CRS program to deliver cargo spacecraft to the ISS.