Doug Hurley and Bob Behnken took part in a farewell ceremony at the International Space Station on Saturday.
It came several hours ahead of their planned departure on a SpaceX Dragon capsule.
Despite Hurricane Isaias approaching the US, Nasa said the weather looks favourable for a Sunday afternoon splashdown in the Gulf of Mexico, near Pensacola, Florida, the new prime site.
It will be the first splashdown for astronauts in 45 years.
The last time was following the joint US-Soviet mission in 1975 known as Apollo-Soyuz.
The astronauts' homecoming will cap a two-month mission that ended a prolonged launch drought in the US, which has relied on Russian rockets to ferry astronauts to the space station since the end of the shuttle era.
In launching Hurley and Behnken from Nasa's Kennedy Space Center on May 30, SpaceX became the first private company to send people into orbit.
Now SpaceX is on the verge of becoming the first company to bring people back from orbit.
"The hardest part was getting us launched, but the most important is bringing us home," Mr Behnken said.
He said a successful splashdown will bring US-crew launching capability "full circle."
Space station commander Chris Cassidy, who will remain on board with two Russians until October, presented Mr Hurley with the small US flag left behind by the previous astronauts to launch to the space station from American soil, in July 2011.
Mr Hurley was the pilot of that final shuttle mission.
The flag — which also flew on the first shuttle flight in 1981 — became a prize for the company that launched astronauts first.
Elon Musk's SpaceX easily beat Boeing, which isn't expected to launch its first crew until next year and will land in the US Southwest.
The flag has one more flight after this one: to the moon on Nasa's Artemis program in the next few years.
Mr Cassiday said: "We're a little sad to see them go but very excited for what it means to our international space program to add this capability" of commercial crew capsules.
The next SpaceX crew flight is targeted for the end of September.
Mr Hurley and MrBehnken also are bringing back a sparkly blue and purple dinosaur named Tremor.
Their young sons chose the toy to accompany their fathers on the historic mission.