SpaceX Crew Dragon Endeavour has 'splashed down' in the Gulf of Mexico on time after re-entering the Earth's atmosphere and deploying its parachutes without any glitches.
Pilot Doug Hurley, one of the two astronauts on board, said: "It's truly our honour and privilege" as radio communications became choppy and cut out.
A number of civilian boats swarmed the landing zone as a recovery ship sped to the scorched capsule and brought it aboard.
But the hatch opening was delayed for some time as a team worked to stop a leak of rocket fuel vapour.
It was the first water landing for a US spacecraft since the Apollo-Soyuz mission of 1975.
Earlier, NASA footage showed the capsule drifting slowly away from the ISS in the darkness of space, ending a two-month stay for the first US astronauts to reach the orbiting lab on an American spacecraft in nearly a decade.
"And they are off!" the US space agency tweeted, with Doug Hurley and Bob Behnken set to splash down to Earth later this evening.
The splash-down site is off the coast of Pensacola, Florida. NASA opted to go ahead with bringing the pair home despite the threat of Isaias, which was downgraded to a tropical storm from a hurricane yesterday.
"Now is the entry, descent and splashdown phase after we undock, hopefully a little bit later today," Mr Hurley said in a farewell ceremony aboard the ISS that was broadcast on NASA TV.
Earlier, during the ISS ceremony, Mr Behnken said that "the hardest part was getting us launched. But the most important part is bringing us home".
Addressing his son and Mr Hurley's son, he held up a toy dinosaur that the children chose to send on the mission and said: "Tremor The Apatosaurus is headed home soon and he'll be with your dads."
Mr Behnken later tweeted: "All my bags are packed, I'm ready to go."
US President Donald Trump tweeted: "Great to have NASA astronauts return to Earth after very successful two month mission. Thank you to all."
Mission chief Chris Cassidy called it an "exciting day" and hailed the importance of having a new means to transport astronauts.
The mission, which blasted off 30 May, marked the first time a crewed spaceship had launched into orbit from American soil since 2011 when the space shuttle programme ended.
Great to have NASA Astronauts return to Earth after very successful two month mission. Thank you to all!— Donald J. Trump (@realDonaldTrump) August 2, 2020
It was also the first time a private company has flown to the ISS carrying astronauts.
The US has paid SpaceX and aerospace giant Boeing a total of about $7bn for their "space taxi" contracts.
But Boeing's programme has floundered badly after a failed test run late last year, which left SpaceX, a company founded only in 2002, as clear frontrunner.
For the past nine years, US astronauts traveled exclusively on Russian Soyuz rockets, for a price of around $80m per seat.