Two plaques that flew on Mir were unveiled
The US space agency Nasa postponed the landing slightly, asking the shuttle to orbit the earth one extra time so that it came in after a storm in Florida.
Earlier, the station's three former crew members said they were sad to leave the ISS but were dreaming about their favourite food when they arrived.
A Russian Progress ship took off from Baikonur in Kazakhstan carrying 2.5 tons of supplies and is expected to dock with the ISS on Thursday.
Russian commander Yuri Usachev and US astronauts James Voss and Susan Helms lived on the ISS for more than five months.
"I think I've been in denial about this whole departure thing and I wasn't really quite ready to go, because I've enjoyed the tour so much on the space station," Ms Helms said on Tuesday.
Food cravings
As soon as she lands, she wants a fresh salad, she said. The former commander Mr Usachev was craving real cheese and real coffee, he said, while Mr Voss was dreaming of a hamburger and ice-cream.
As well as bringing home the second crew, the shuttle will return the Italian-built Leonardo logistics module to Earth.
Discovery left behind the new Expedition Three crew members - US commander Frank Culbertson and Russian cosmonauts Vladimir Dezhurov and Mikhail Tyurin.
The trio, who will remain at the ISS for four months, are the third crew to live on the station.
The new residents will work on 40 or more planned US and Russian experiments, until they leave in December.
Research will be conducted to look at the effect of space travel on the body, in order to better understand how certain illnesses affect the organs of patients.