Handshake between the two robotic arms
Californian businessman Dennis Tito is now due to arrive at the station at 0900BST on Monday with Russian cosmonauts Talgat Musbayev and Yuri Baturin.
The Endeavour's departure comes a day after engineers finally revived a backup computer needed to operate a new billion-dollar robotic arm on the ISS.
The 17.5 metre (58-foot) arm was used to complete what has been billed by Nasa as the most complicated robotic feat ever attempted in space - transferring a 1.5-tonne packaging crate to Endeavour's own smaller arm.
The shuttle arm then placed the crate in Endeavour's cargo bay ready to return to Earth.
With that maneouvre completed, the shuttle and its seven crew members departed from the ISS.
"Goodbye and we wish you a happy landing," astronaut Susan Helms called out from the station's laboratory module as the Endeavour left.
'Incredible adventure'
Before leaving the ISS for good, Endeavour pilot Jeff Ashby backed the shuttle about 137 metres away so that the crew could take Imax pictures of the complex with Earth in the background.
Ashby said: "It's been an incredible adventure and a great mission to be on up here at the International Space Station.
"We're a little bit sad to be leaving, but also anxious to turn around and head back home to see our families."
Nasa says all three of the command and control computers needed to operate the robotic arm are functioning, although the two back-up machines have hard drive problems.
'Happy people'
Staff praised the astronauts for their part in carrying out the repairs.
"It was a lot of work getting to this point, and there's a whole lot of really, really happy people down here on the ground," lead shuttle flight director Phil Engelauf told the astronauts.
"We'll have a couple of cold ones when you back and swap stories."
Mission Control has now relieved the ISS crew of almost all its duties while ground engineers test the computers.
They shall now have plenty of time to "entertain" the Soyuz visitors, according to Nasa official Bob Cabana.
Nasa fears
The main aim of the Soyuz mission - which blasted off from the Baikonur cosmodrome in Kazakhstan on Saturday - is to replace an existing capsule already docked to the ISS.
Travelling with two cosmonauts is the 60-year-old Mr Tito, who is reported to have paid $20m for the privilege of becoming the first ever space tourist.
It was only in the days before take-off that Nasa finally lifted objections to Mr Tito's trip, having expressed fears that his presence could jeopardise the safety of the ISS.
In order to win Nasa's approval, Mr Tito had to sign an agreement that he would not wander through American segments of the ISS without an escort. He also agreed to pay for any breakages.