Resilience launched on 16 November 2020 at 00:27:17 UTC[9][c] on a Falcon 9 from Kennedy Space Center Launch Complex 39A (LC-39A), carrying NASA astronauts Michael Hopkins, Victor Glover and Shannon Walker, along with JAXA astronaut Soichi Noguchi, all members of the Expedition 64 crew.

Following the Crew Dragon Demonstration Mission 2, Crew-1 was tentatively scheduled for September 2020; further delays occurred to align with the ongoing COVID-19 pandemic restrictions and their impact on the schedule of ISS crew rotations and cargo delivery missions,[16] and then again because of concerns about an issue with the gas generators on the Merlin 1D engines.

[19] On 29 September 2020, mission commander Michael Hopkins revealed during a NASA press conference that the capsule's crew had chosen to name it Resilience.

[20] Due to the COVID-19 pandemic in Florida, the Kennedy Space Center Visitor Complex only allowed a few people to watch the launch in person from the KSC premises.

[30] The launch vehicle was lifted to its vertical position on the pad for a test firing of its Merlin-1D main engines on 11 November 2020 at 20:49 UTC.

[31] A dry dress rehearsal (DDR) on 12 November 2020 saw the crew put on their pressure suits and climb into Resilience.

Its Falcon 9 first-stage booster, SN B1061.1, landed on the autonomous spaceport drone ship Just Read the Instructions.

For this mission, the crew had chosen a plush toy of "The Child" (also known as "Baby Yoda") from The Mandalorian as a Zero-G indicator.