The world's first lunar visitors orbited the moon on Apollo 8. The Artemis II crew will instead go around the moon in an out-and-back slingshot.
NASA said it expected the return trip to end at about 5:57 p.m., when the Dragon is scheduled to splash down off the Florida coast.
The Crew-10 mission, part of a routine staff rotation jointly operated by NASA and SpaceX, took off at 7:03 p.m. ET Friday from Kennedy Space Center in Florida.
SpaceX postponed a mission on Wednesday to bring the next crew set to work on the International Space Station (ISS) and begin the return of a pair of astronauts back to Earth.
Elon Musk recently called for the ISS to be deorbited "as soon as possible." Experts say the station provides vital research, technological development and education.
The best view of Hurricane Milton may come from 250 miles above Earth.