Commander Lee Archambault guided Discovery onto the runway, touching down shortly before 3.15pm EDT (1915 GMT).
NASA officials delayed plans for an earlier landing due to gathering clouds and gusting winds, forcing another orbit of Earth.
The shuttle's mission to the International Space Station included the delivery of a fourth and final set of solar panel wings.
Crew member Koichi Wakata stayed behind, the first Japanese astronaut to live on the orbital outpost.